Bulking diet, critique please

[DrBobbo]

As a quick introduction before everyone starts ripping apart the flaws in my diet -- I'm a college student,
so bear in mind that sometimes I have difficulty fitting in 8 meals a day, so I had to put together a diet
that still meets my nutritional needs, but also affords me the time to go to a full time schedule's worth of
classes and work in between. My stats are 20 years old, 5'11", 190 lbs, approx 9% BF, been lifting natural for about 8
months. I drink about 1.5 gallons of water a day, supplement with a multi vitamin w/ b complex after I wake
up and before I go to bed, flax and fish oil, and I try to take some vitamin c before workouts. Anyway I'm sure
I'm leaving something out, so I'll just post the diet:

[8:30 am] meal #1
2 cups (measured uncooked) oats
whey in milk (50g protein)

[12:30 pm] meal #2
turkey sandwich on whole wheat (40g protein)
glass of skim milk

[2:30-3:20 pm] lift

[3:30 pm] meal #3 (post workout)
whey shake in gatorade (100g dextrose, 50g protein)

[4:30 pm] meal #4
roast beef on whole wheat (40g protein)
glass of skim milk

[7:30 pm] meal #5
*breaded chicken fingers (50g or more protein)

[10:30 pm] meal #6
whey in no fat no carb milk (50g protein)

*yeah this meal is kind of difficult to avoid since no other dining halls are open. My only other option here would
be a greasy calzone with little protein, fried chicken wings, or eating in (which I often do if I have clean food)

Critique away :thumbsup:

 

[goldylight]

for college that aint bad. how are you ding with fat gain? what do you think your body fat % is right now? i would try to switch out some of the bread with oatmeal. oatmeal is real cheap and all you need is hot water. for your post workout - i would cut the gatorade in half at least, if not totally switching it out for oatmeal. before bed, add some flax oil with that shake. whey digests very quickly, so if you can sub that out before bed with either cottage cheese or a slow digesting protein that would e great.

 

[DrBobbo]

for college that aint bad. how are you ding with fat gain? what do you think your body fat % is right now? i would try to switch out some of the bread with oatmeal. oatmeal is real cheap and all you need is hot water. for your post workout - i would cut the gatorade in half at least, if not totally switching it out for oatmeal. before bed, add some flax oil with that shake. whey digests very quickly, so if you can sub that out before bed with either cottage cheese or a slow digesting protein that would e great.

I gain fat pretty slowly on this diet, usually wont notice a fat increase for a few months. Completely drop gatorade (dextrose) from my post workout shake? Hmm I was always told that it was a critical part of a post workout drink. Any more opinions on this?

 

[goldylight]

yes there has been many debates on this topic at this very board. do a search for it - basically saying low gi will do exactly what you need for post workout without the sugar(sugar=fat).

 

[Kristopher]

yeah but dextrose incurs a better/quicker insulin response needed for post workout needs..

 

[Kristopher]

btw looks like you need more cals..

 

[Dwight Schrute]

yeah but dextrose incurs a better/quicker insulin response needed for post workout needs..

Post workout "needs" do not require a fast insulin response.

 

[tattoopierced1]

I would add something between meal 1 and meal 2 as well, possibly some turkey bacon for some quick protein and calories.

 

[goldylight]

yeah but dextrose incurs a better/quicker insulin response needed for post workout needs..

you be wrong brudda. especially if pre workout nutrition is up to par.

 

[DrBobbo]

how about some natty pb and a can of tuna in between meal 1 and 2

 

[Edge]

Im still trying to figure out how you can stomach whey protein IN gatorade! yuck! Chocolate Tropical Punch! :icon_lol:

 

[DrBobbo]

Im still trying to figure out how you can stomach whey protein IN gatorade! yuck! Chocolate Tropical Punch! :icon_lol:

haha I'll eat / drink anything for gains. I used to drink egg beaters for breakfast until I got sick of them.

 

[goldylight]

natty pb is great for cals. puts too much fat on me personally. banannas are good too. van of tuna, few tbsp of pb and a banana and you are set. add cals whenever\wherever you can.

 

[goldylight]

another good thing for extra cals thats cheap is to try to down btw 1/2 a gallon and a gallon of skim milk if your stomach can handle it. its cheap and works great.

 

[DrBobbo]

another good thing for extra cals thats cheap is to try to down btw 1/2 a gallon and a gallon of skim milk if your stomach can handle it. its cheap and works great.

\
yeah I worked at a supermarket over the summer and I was drinking quarts of low carb milk everyday, definitely helped. should probably go pick up some skim too for morning hours.

 

[LunaHotel]

Post workout "needs" do not require a fast insulin response.

Wrong. A fast insulin response is CRITICAL to growth, as exercise-induced GH release is very short-lived. He DOES want his GH turned into IGF-1, doesn't he?

 

[Dwight Schrute]

I suggest you do a bit more research.



Physiological hyperinsulinemia stimulates p70(S6k) phosphorylation in human skeletal muscle.

Hillier T, Long W, Jahn L, Wei L, Barrett EJ.

Department of Internal Medicine, Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

Using tracer methods, insulin stimulates muscle protein synthesis in vitro, an effect not seen in vivo with physiological insulin concentrations in adult animals or humans. To examine the action of physiological hyperinsulinemia on protein synthesis using a tracer-independent method in vivo and identify possible explanations for this discrepancy, we measured the phosphorylation of ribosomal protein S6 kinase (P70(S6k)) and eIF4E-binding protein (eIF4E-BP1), two key proteins that regulate messenger ribonucleic acid translation and protein synthesis. Postabsorptive healthy adults received either a 2-h insulin infusion (1 mU/min.kg; euglycemic insulin clamp; n = 6) or a 2-h saline infusion (n = 5). Vastus lateralis muscle was biopsied at baseline and at the end of the infusion period. Phosphorylation of P70(S6k) and eIF4E-BP1 was quantified on Western blots after SDS-PAGE. Physiological increments in plasma insulin (42 +/- 13 to 366 +/- 36 pmol/L; P: = 0.0002) significantly increased p70(S6k) (P: < 0.01), but did not affect eIF4E-BP1 phosphorylation in muscle. Plasma insulin declined slightly during saline infusion (P: = 0.04), and there was no change in the phosphorylation of either p70(S6k) or eIF4E-BP1. These findings indicate an important role of physiological hyperinsulinemia in the regulation of p70(S6k) in human muscle. This finding is consistent with a potential role for insulin in regulating the synthesis of that subset of proteins involved in ribosomal function. The failure to enhance the phosphorylation of eIF4E-BP1 may in part explain the lack of a stimulatory effect of physiological hyperinsulinemia on bulk protein synthesis in skeletal muscle in vivo.


Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle.

Liu Z, Jahn LA, Wei L, Long W, Barrett EJ.

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. [email protected]

Studies in vitro as well as in vivo in rodents have suggested that amino acids (AA) not only serve as substrates for protein synthesis, but also as nutrient signals to enhance mRNA translation and protein synthesis in skeletal muscle. However, the physiological relevance of these findings to normal humans is uncertain. To examine whether AA regulate the protein synthetic apparatus in human skeletal muscle, we infused an AA mixture (10% Travesol) systemically into 10 young healthy male volunteers for 6 h. Forearm muscle protein synthesis and degradation (phenylalanine tracer method) and the phosphorylation of protein kinase B (or Akt), eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein S6 kinase (p70(S6K)) in vastus lateralis muscle were measured before and after AA infusion. We also examined whether AA affect urinary nitrogen excretion and whole body protein turnover. Postabsorptively all subjects had negative forearm phenylalanine balances. AA infusion significantly improved the net phenylalanine balance at both 3 h (P < 0.002) and 6 h (P < 0.02). This improvement in phenylalanine balance was solely from increased protein synthesis (P = 0.02 at 3 h and P < 0.003 at 6 h), as protein degradation was not changed. AA also significantly decreased whole body phenylalanine flux (P < 0.004). AA did not activate Akt phosphorylation at Ser(473), but significantly increased the phosphorylation of both eukaryotic initiation factor 4E-binding protein 1 (P < 0.04) and p70(S6K) (P < 0.001). We conclude that AA act directly as nutrient signals to stimulate protein synthesis through Akt-independent activation of the protein synthetic apparatus in human skeletal muscle.

Amino acids regulate skeletal muscle PHAS-I and p70 S6-kinase phosphorylation independently of insulin. Long, W., L. Saffer, L. Wei, and E. J. Barrett. Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
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APStracts 7:0077E, 2000.
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Refeeding reverses the muscle protein loss seen with fasting. The physiological regulators and cellular control sites responsible for this reversal are incompletely defined. Phosphorylation of phosphorylated heat-acid stabled protein (PHAS-I) frees eukaryotic initiation factor 4E (eIF4E) and stimulates protein synthesis by accelerating translation initiation. Phosphorylation of p70 S6-kinase (p70S6k) is thought to be involved in the regulation of the synthesis of some ribosomsal proteins and other selected proteins with polypyrimidine clusters near the transcription start site. We examined whether phosphorylation of PHAS-I and p70S6k was increased by feeding and determined the separate effects of insulin and amino acids on PHAS-I and p70S6k phosphorylation in rat skeletal muscle in vivo. Muscle was obtained from rats fed ad libitum or fasted overnight (n = 5 each). Other fasted rats were infused with insulin (3 muU�min�minus�1�kg�minus�1, euglycemic clamp), amino acids, or the two combined. Gastrocnemius was freeze-clamped, and PHAS-I and p70S6k phosphorylation was measured by quantifying the several phosphorylated forms of these proteins seen on Western blots. We observed that feeding increased phosphorylation of both PHAS-I and p70S6k (P < 0.05). Infusion of amino acids alone reproduced the effect of feeding. Physiological hyperinsulinemia increased p70S6K (P < 0.05) but not PHAS-I phosphorylation (P = 0.98). Addition of insulin to amino acid infusion was no more effective than amino acids alone in promoting PHAS-I and p70S6k phosphorylation. We conclude that amino acid infusion alone enhances the activation of the protein synthetic pathways in vivo in rat skeletal muscle. This effect is not dependent on increases in plasma insulin and simulates the activation of protein synthesis that accompanies normal feeding.

 

[Dwight Schrute]

Wrong. A fast insulin response is CRITICAL to growth, as exercise-induced GH release is very short-lived. He DOES want his GH turned into IGF-1, doesn't he?

GH secretions last up until 60 minutes post exercise. You know what diminishes GH? Insulin. GH is more lipolytic that anything.


Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes.

Deyssig R, Frisch H, Blum WF, Waldhor T.

Department of Paediatrics, University of Vienna, Austria.

The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4 +/- 0.5 years; ideal body weight 122 +/- 3.1%, body fat 10.1 +/- 1.0%; mean +/- SEM) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)-1 day-1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding proteins, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Also its not IGF-1 that contributes to increase muscle growth, it is MGF within localized skeletal muscle.

 

[Dwight Schrute]

Might want to read this one too:


Determinants of post-exercise glycogen synthesis during short-term recovery.

Jentjens R, Jeukendrup A.

Human Performance Laboratory, School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham, UK.

The pattern of muscle glycogen synthesis following glycogen-depleting exercise occurs in two phases. Initially, there is a period of rapid synthesis of muscle glycogen that does not require the presence of insulin and lasts about 30-60 minutes. This rapid phase of muscle glycogen synthesis is characterised by an exercise-induced translocation of glucose transporter carrier protein-4 to the cell surface, leading to an increased permeability of the muscle membrane to glucose. Following this rapid phase of glycogen synthesis, muscle glycogen synthesis occurs at a much slower rate and this phase can last for several hours. Both muscle contraction and insulin have been shown to increase the activity of glycogen synthase, the rate-limiting enzyme in glycogen synthesis. Furthermore, it has been shown that muscle glycogen concentration is a potent regulator of glycogen synthase. Low muscle glycogen concentrations following exercise are associated with an increased rate of glucose transport and an increased capacity to convert glucose into glycogen.The highest muscle glycogen synthesis rates have been reported when large amounts of carbohydrate (1.0-1.85 g/kg/h) are consumed immediately post-exercise and at 15-60 minute intervals thereafter, for up to 5 hours post-exercise. When carbohydrate ingestion is delayed by several hours, this may lead to ~50% lower rates of muscle glycogen synthesis. The addition of certain amino acids and/or proteins to a carbohydrate supplement can increase muscle glycogen synthesis rates, most probably because of an enhanced insulin response. However, when carbohydrate intake is high (>/=1.2 g/kg/h) and provided at regular intervals, a further increase in insulin concentrations by additional supplementation of protein and/or amino acids does not further increase the rate of muscle glycogen synthesis. Thus, when carbohydrate intake is insufficient (<1.2 g/kg/h), the addition of certain amino acids and/or proteins may be beneficial for muscle glycogen synthesis. Furthermore, ingestion of insulinotropic protein and/or amino acid mixtures might stimulate post-exercise net muscle protein anabolism. Suggestions have been made that carbohydrate availability is the main limiting factor for glycogen synthesis. A large part of the ingested glucose that enters the bloodstream appears to be extracted by tissues other than the exercise muscle (i.e. liver, other muscle groups or fat tissue) and may therefore limit the amount of glucose available to maximise muscle glycogen synthesis rates. Furthermore, intestinal glucose absorption may also be a rate-limiting factor for muscle glycogen synthesis when large quantities (>1 g/min) of glucose are ingested following exercise.

 

[Dwight Schrute]

Forgot this one too:

Carbohydrate nutrition before, during, and after exercise.

Costill DL.

The role of dietary carbohydrates (CHO) in the resynthesis of muscle and liver glycogen after prolonged, exhaustive exercise has been clearly demonstrated. The mechanisms responsible for optimal glycogen storage are linked to the activation of glycogen synthetase by depletion of glycogen and the subsequent intake of CHO. Although diets rich in CHO may increase the muscle glycogen stores and enhance endurance exercise performance when consumed in the days before the activity, they also increase the rate of CHO oxidation and the use of muscle glycogen. When consumed in the last hour before exercise, the insulin stimulated-uptake of glucose from blood often results in hypoglycemia, greater dependence on muscle glycogen, and an earlier onset of exhaustion than when no CHO is fed. Ingesting CHO during exercise appears to be of minimal value to performance except in events lasting 2 h or longer. The form of CHO (i.e., glucose, fructose, sucrose) ingested may produce different blood glucose and insulin responses, but the rate of muscle glycogen resynthesis is about the same regardless of the structure.

 

[Deano]

Bobo, i may be wrong but does mean that it is better to not eat carbs before training?
"When consumed in the last hour before exercise, the insulin stimulated-uptake of glucose from blood often results in hypoglycemia, greater dependence on muscle glycogen, and an earlier onset of exhaustion than when no CHO is fed."

That is what it sounds like to me but like i said i might be wrong.

DEANO

 

[Dwight Schrute]

If the amount is great and the GI is high then yes you could have a negative result (think about taking in a lot of sugar then how you feel 45 minutes later). Thats why a low-mod GI is preferential because it controls blood glucose and insulin much better and will prevent any type of crash from the result of a large amount of high GI carbs.

And remember the exercise that they are referring to is prolonged exaustive exercise. THe hormonal release is different for that type of exercise than resistant training. In fact it is much worse in terms of catabolic activity so this shows even when you are REALLY depleted the form of CHO really doesn't matter when it comes to glycogen resynthesis.


Now the other studies show the results of short term recovery and the conlcusion is amino acids are MUCH more important the any physiological insulin release.

Remember the primary role of insulin it to shuttle nutrients. It does this by increasing GLUT4 receptors and increasing cell permeability. Now during normal feeding patterns this is very true but during exercise the need for it minimal because exercise in itself does this all alone and much moreso than insulin, so there is need for a high spike and large amount at one given time. In fact the study even states the majority of glucose does not get shuttled to the exercised muscle BECAUSE of this.

 

[LunaHotel]

That's all well and good, friend, but that's not what I am talking about. Your studies are of course correct, but miss the point completely.

YOU do a little more research, because you don't seem to know that insulin being released WHILE GH IS HIGH makes the liver turn it into IGF-1 and is the only way to do so. Or maybe you don't know that IGF-1 is anabolic? Or maybe you don't know that weight training releases GH? Or maybe you don't know that glycogen sythesis, protein synthesis, satellite-cell hyperplasia, and merging of those cells are all PART of muscle growth but are NOT equivalent? I don't know which specific things of these you don't know, but do read up, please.

I know it's not easy to be confronted with such a veritable behemoth of knowledge as I, but it was ever thus : destruction of beliefs causes great anguish, pain and protests. But in the end, whole truth in science prevails.

 

[Dwight Schrute]

That's all well and good, friend, but that's not what I am talking about. Your studies are of course correct, but miss the point completely.

YOU do a little more research, because you don't seem to know that insulin being released WHILE GH IS HIGH makes the liver turn it into IGF-1 and is the only way to do so. Or maybe you don't know that IGF-1 is anabolic? Or maybe you don't know that weight training releases GH? Or maybe you don't know that glycogen sythesis, protein synthesis, satellite-cell hyperplasia, and merging of those cells are all PART of muscle growth but are NOT equivalent? I don't know which specific things of these you don't know, but do read up, please.

I know it's not easy to be confronted with such a veritable behemoth of knowledge as I, but it was ever thus : destruction of beliefs causes great anguish, pain and protests. But in the end, whole truth in science prevails.

Hey genius, maybe you should research a bit more because what happens when circulating hepatic IGF-1 is increased? IGFBP3 is increased rendering is USELESS. The body keeps a constant homeostasis between the GH/GF-1 axis. That is why rIGF-1 injected does not work much because the body counteracts it by increasing the binding protein. That is WHY Gropep introduced Long R3 IGF-1 BECAUSE it resists the IGFBP3.


And this would be confirmed by this statement in a study which you obvisouly didn't read.

"The failure to enhance the phosphorylation of eIF4E-BP1 may in part explain the lack of a stimulatory effect of physiological hyperinsulinemia on bulk protein synthesis in skeletal muscle in vivo."

MGF causes the increases skleletal muscle not hepatic IGF-1 and this occurs over LONG peroids of time. I suggest you look up the effects of increasing eccentric time and MGF.


So go hit the books again and stop repeating what every other message board says.

 

[Dwight Schrute]

Or maybe you don't know that glycogen sythesis, protein synthesis, satellite-cell hyperplasia, and merging of those cells are all PART of muscle growth but are NOT equivalent? I don't know which specific things of these you don't know, but do read up, please.

Satellite cell hypersplasia won't be much of a factor unless supraphysiolgical levels are given exogenously for long peroids of time. There is a reason why in vitro studies show different results than in vivo studies.

I suggest you learn the difference.

 

[Dwight Schrute]

"GH and nsulin do act synergistically in the sense that insulin responsiveness is required for GH to exert any growth promoting action, but keep in mind that the main action of insulin is to antagonize the action of GH.

For starters, insulin inhibits GH release (1)

Insulin also accelerates GH clearance from the blood (2) and lowers levels of the potent GH secreatagogue ghrelin (3).

These all contribute the the GH dysfunction seen in obesity and insulin resistance.


The second article you cited pointed out that "Insulin induced a concentration-dependent increase in GHR biosynthesis, but simultaneously inhibited surface translocation. However, the net effect of reducing receptor surface availability only occurred at concentrations greater than 10 nmol/L, a concentration causing 70% inhibition of surface translocation."

So insulin is both increasing receptor production but blocking movement of the newly synthesized receptor to the cell surface where they must be located to bind to GH. At high insulin concentrations (10nM/L) the second effect dominates so the high insulin levels are interfering with GH signaling.

The liver is also special. In other tissues insulin has no effect on GH receptor production, but has the same blocking effect on GH receptor surface translocation as seen in the liver, which inhibits the ability of the GH receptor to bind GH. So again we see an inhibitory effect of insulin on GH signaling:

http://www.pnas.org/cgi/content/full/94/21/11381

Also recall that GH treatment typically induces insulin resistance and consequently hyperinsulinemia. The elevated insulin levels downregulate insulin receptor expresession and interfere with insulin signaling (4). So once again we see a reciprocal inhibitory action between GH and insulin


(1) Metabolism 1999 Sep;48(9):1152-6

Elevated insulin levels contribute to the reduced growth hormone (GH) response to GH-releasing hormone in obese subjects.

Lanzi R, Luzi L, Caumo A, Andreotti AC, Manzoni MF, Malighetti ME, Sereni LP, Pontiroli AE.

(2) J Clin Endocrinol Metab 2002 May;87(5):2185-93

Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age.

Hansen TK, Jorgensen JO, Christiansen JS

(3) Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E313-6.

The influence of insulin on circulating ghrelin.

Flanagan DE, Evans ML, Monsod TP, Rife F, Heptulla RA, Tamborlane WV, Sherwin RS.

(4) Exp Biol Med (Maywood). 2002 Mar;227(3):149-57.

Growth hormone-induced alterations in the insulin-signaling system.

Dominici FP, Turyn D."


"Would also like to add that insulin and GH are regulated in different fashion because of the GH - IGF-1 axis. IGF-1 has many effects similar to insulin, so in order to remain healthy it is probably beneficial not to have excess insulin at the time of an IGF-1 surge.

The differential regulation of insulin and IGF-1 and the difference in their receptor count and location also accounts for a lot of IGF's effects on improving body-fat characteristics, despite being inherently adipogenic."

 

[Dwight Schrute]

I don't know which specific things of these you don't know, but do read up, please.

I know it's not easy to be confronted with such a veritable behemoth of knowledge as I, but it was ever thus : destruction of beliefs causes great anguish, pain and protests. But in the end, whole truth in science prevails.

Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged
Jonas NYGREN*, Anders THORELL*, Kerstin BRISMAR�*, Pia ESSÉN‡, Jan WERNERMAN‡, Margaret A. MCNURLAN§, Peter J. GARLICK§ and Olle LJUNGQVIST*

*Centre for Gastrointestinal Disease, Ersta Hospital, Karolinska Institute, 116 91 Stockholm, Sweden, �*Department of Endocrinology, Karolinska Hospital, Karolinska Institute, 171 76 Stockholm, Sweden, ‡Department of Anaesthesia, Huddinge University Hospital, Karolinska Institute, 141 86 Stockholm, Sweden, and §Department of Surgery, State University of New York, Stony Brook, NY 11794, U.S.A.

Key words: glucose clamp technique, glucose metabolism, growth hormone, insulin resistance, protein metabolism.

Abbreviations: GH, growth hormone; IGF, insulin-like growth factor; IGFBP, IGF-binding protein; M/I ratio, mean level of glucose infusion/mean serum insulin level; NEFA, non-esterified fatty acids.

Correspondence: Dr Jonas Nygren, Centre for Gastrointestinal Disease, Ersta Hospital, Box 4622, 116 91 Stockholm, Sweden (e-mail [email protected]).

The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05mg·24h-1·kg-1) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[2H5]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P < 0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P < 0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P < 0.05). In addition, 24h urinary nitrogen excretion decreased by 26% (P < 0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P < 0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.

INTRODUCTION

It is generally believed that most of the anabolic actions of growth hormone (GH) are mediated by insulin-like growth factor-I (IGF-I). However, GH also exerts metabolic effects directly on tissues, while IGF-I may enhance or counteract the direct metabolic effects of GH. In addition, the effect of IGF-I is dependent on its binding to specific binding proteins, since mainly the free form of IGF-I is metabolically active [ 1]. This makes the effect of the GH/IGF-I axis on metabolism difficult to study, to some extent explaining the contradictory results found in some previous studies. Thus intracellular rates of oxidation of glucose and fat, as well as protein synthesis rates in skeletal muscle, were reported to be affected by GH in some studies [ 2–4], but not in others [ 5–8].

An important difference between the direct and indirect (through IGF-I) effects of GH relates to insulin sensitivity. GH is known to induce insulin resistance, whereas IGF-I has insulin-like effects on glucose and protein metabolism. Although GH-induced insulin resistance has been studied over the years, the mechanism responsible for this condition is still not clear. Inconsistencies with regard to the effects of GH treatment on glucose and protein metabolism may be attributed to the relationship between the direct and indirect effects of GH, as well as to methodological issues. Insulin resistance has been studied mainly by the use of the hyperinsulinaemic normoglycaemic clamp [ 9]. However, since glucose flux is reduced in states of insulin resistance, this will also automatically affect intracellular substrate utilization and reduce glucose oxidation. If insulin rather than glucose infusion rates (as used in the classical clamp technique) were adjusted during the clamp, this alternative technique would test whether the normalization of glucose flux could also correct other insulin-sensitive metabolic pathways.

The aim of the present study was to investigate the relationship between the decrease in insulin sensitivity that accompanies treatment with GH and intracellular substrate oxidation rates measured while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Thus similar glucose flux was maintained before and after GH treatment, and protein synthesis rates in skeletal muscle were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in substrate oxidation, energy requirements, protein synthesis rates, nitrogen balance, urinary 3-methylhistidine excretion, body composition and the hormonal milieu.

METHODS

Subjects

Six healthy male volunteers (age 22±1 years; body mass index 23±1kg/m2) participated in the study. None had a history or clinical evidence of medical illness, and none was taking any medication. Informed consent was obtained from each volunteer before participation in the study, which was reviewed and approved by the Institutional Ethical Committee.

Experimental design

The subjects underwent the same study protocol twice. The first study represents a control situation, before treatment. Then, 2–4 weeks later, the same hyperinsulinaemic normoglycaemic clamp protocol was repeated after a treatment period of 5 daily subcutaneous injections of human recombinant GH (0.05mg·24h-1·kg-1; Genotropin®, kindly donated by Kabi Vitrum, Stockholm, Sweden), administered at 08.00hours. The second hyperinsulinaemic normoglycaemic clamp was performed on the sixth day. Before entering the study, the resting energy expenditure of each subject was determined using indirect calorimetry (Deltatrac®; Dansjö, Stockholm, Sweden). For the 3 days preceding each clamp study, each subject was given a standardized diet (46% carbohydrate, 41% fat and 15% protein) with an energy content of 135% of their measured resting energy expenditure. The diet provided a fixed 10460kJ (2500kcal)/24h, and the remaining energy was provided as a drink [Semper standard®; 502kJ (120kcal)/100ml; 53% carbohydrate, 30% fat and 17% protein]. During the 3 days of controlled food intake, urine was collected in 24h portions for analyses of total nitrogen excretion and 3-methylhistidine excretion. Total urinary nitrogen excretion was determined using a chemoluminescence nitrogen analyser [ANTEK 720/771®; Edect (Scientific) Ltd, Hargrave, Northhamptonshire, U.K.]. Nitrogen balance was calculated as:

Urinary 3-methylhistidine excretion was measured by HPLC [ 10].

Euglucaemic clamp

At 08.00hours, after the subject had fasted overnight, a hyperinsulinaemic normoglycaemic clamp was performed using an artificial pancreas (Biostator®; Life Science Instruments, Elkhart, IN, U.S.A.) as described previously [ 11]. Arterialization of venous blood was attained using a thermoregulated sleeve (Kanthal; Medical Heating ASB, Stockholm, Sweden) on both arms, set at 45°C [ 12]. The subjects were given a continuous infusion of 20% (w/v) glucose (Kabi Pharmacia, Uppsala, Sweden) in a two-step manner (2 and 5mg·min-1·kg-1) for 120min at each rate. Normoglycaemia was maintained by a variable infusion of insulin (Actrapid Human®; Novo, Copenhagen, Denmark). Steady-state conditions were attained after approx. 60min of insulin and glucose infusion, and the glucose clamp was maintained for another 60min at each level of glucose infusion. During the two periods of steady state, the mean insulin infusion rate required to maintain normoglycaemia was calculated (m-units·min-1·kg-1). The mean level of glucose infusion divided by the mean serum insulin level (M/I ratio) at each level of glucose infusion was used as a measurement of whole-body insulin sensitivity.

Blood sampling and analysis

Blood samples were taken for substrate and hormone determinations in the basal state prior to glucose infusion. Sampling was also performed during the normoglycaemic clamps at 30min intervals during the last 60min of each level of glucose infusion (i.e. at 60, 90, 120, 180, 210 and 240min). All samples were placed on ice; serum samples were allowed to clot before separation, while plasma samples were centrifuged immediately for 10min at 4°C at 2010g and the aliquots were stored at -20°C until batch analysis. Blood glucose was determined by a glucose analyser (model 23 AM; Yellow Springs Instruments) using the glucose peroxidase method [ 13]. Determinations of insulin [ 14], glucagon [ 15], IGF-I [ 16], IGF-binding protein-1 (IGFBP-1) [ 17] and IGFBP-3 [ 18] were performed using RIA techniques. C-peptide was analysed using a commercially available kit (Hoechst, Frankfurt, Germany). GH was analysed using a fluoroimmunoassay kit [ 19], while catecholamines were determined by HPLC and electrochemical detection [ 20]. Non-esterified ('free') fatty acids (NEFA) were analysed using a radiochemical assay [ 21].

Indirect calorimetry

This was performed with a hood calorimeter (Deltatrac®) [ 22] before glucose infusion and during the last 30min of steady state at both levels of glucose infusion. After excluding the part required for protein oxidation (calculated from urinary nitrogen excretion), respiratory quotients, energy expenditure and oxidation rates for glucose and fat were calculated [ 23].

Protein synthesis

The determination of protein synthesis rates in human skeletal muscle using the flooding technique has been described previously [ 24, 25]. The protein synthesis measurements, with a study protocol of 90min, were performed at the end of the glucose clamp measurement (i.e. 240–330min), while maintaining a glucose infusion rate of 5mg·min-1·kg-1 and a variable insulin infusion to obtain normoglycaemia. Measurements were obtained following a 10min intravenous injection of [2H5]phenylalanine (45mg/kg; 7.5mol% excess at the first measurement and 15mol% excess at the second measurement; Mass Trace Inc., Somerville, MA, U.S.A.). Blood samples were taken from a venous line in the opposite arm to that used for glucose and insulin infusion [ 11] at 0, 5, 10, 15, 30, 60 and 90min after the phenylalanine injection, for determination of the isotope enrichment of phenylalanine in plasma. At 90min after the isotope injection, a muscle biopsy was taken percutaneously from the lateral portion of the quadriceps femoris muscle using a Bergström needle [ 26] and was frozen immediately in liquid nitrogen.

The determination of L-[2H5]phenylalanine enrichment in plasma samples, as well as in samples of hydrolysed muscle protein, was carried out by GC-MS with electron-impact ionization and selective ion monitoring. The enrichment in plasma was measured by monitoring the ions at m/z 336 and 341 of the tertiary butyldimethylsilyl derivative [ 27]. The enrichment of phenylalanine from protein hydrolysates was measured by enzymic decarboxylation to phenylethylamine, followed by GC-MS of the heptafluorobutyryl derivative at m/z 106 and 109 [ 27]. The determinations were performed on a Fisons MD800 quadropole mass spectrometer. The rates of protein synthesis were calculated from the enrichments of phenylalanine in protein and the free phenylalanine in plasma, as described previously [ 24, 25].

Whole-body impedance measurements

Immediately before the first injection of GH and again 24h after the last injection of GH, before beginning the second clamp, whole-body impedance measurements were performed using a body impedance analyser (BIA-101/S; AKERN srl, Florence, Italy) [ 28]. Both measurements were performed at 08.00hours after an overnight fast, with the subject in a relaxed supine position with arms and legs apart in a slightly abducted manner. The right hand and right foot were used, and the sensing electrodes were placed on an imaginary line bisecting the hand and foot articulations, while the active electrodes were placed at the root of the fingers and toes respectively. After reading values for resistance and reactance, body composition was calculated using software (RJL Systems, Detroit, MI, U.S.A.) connected to a PC-compatible computer.

Statistics

Results are presented as means±S.E.M. Statistical significance was accepted at P<0.05 using two-way ANOVA (entering mean levels obtained during baseline, low and high clamp levels, and before and after treatment into the equation) and least significant difference as post-hoc testing. Wilcoxon's signed rank test (two tailed) was used for analysis of whole-body impedance data. Correlations between data were calculated using simple regression analysis.

RESULTS

Substrates and hormones

Basal blood glucose levels remained unchanged, whereas NEFA levels decreased, after GH treatment (P<0.001) ( Table 1). Basal insulin levels tended to be elevated after GH treatment (P=0.06), while C-peptide levels increased significantly (P<0.01). Basal levels of IGF-I increased 2-fold (P<0.001) and IGFBP-3 displayed an 84% increase after GH treatment (P<0.001). Basal levels of GH, IGFBP-1 and glucagon did not change after treatment ( Table 1). Levels of adrenaline and noradrenaline did not change in response to GH treatment (results not shown).

Effects of GH treatment on substrate and hormone levels in healthy subjects

The subjects (n = 6) underwent a clamp study twice, before and after 5 days of daily single subcutaneous injections of GH (0.05mg·24h-1·kg-1). The clamp involved predetermined glucose infusion rates of 2 and 5mg·min-1·kg-1, with a variable infusion of insulin given in order to maintain normoglycaemia. Values are given as means (S.E.M.). Significance of differences: **P < 0.01, ***P < 0.001 compared with control, using two-way ANOVA for repeated measurements, and least significant difference as post hoc test.
Glucose infusion
Substrate/hormone Basal 2mg·min-1·kg-1 5mg·min-1·kg-1
Blood glucose (mmol/l) Control 4.5(0.1) 4.5(0.2) 4.6(0.2)
GH 4.7(0.1) 4.6(0.1) 4.8(0.2)
Plasma NEFA (µmol/l) Control 557(33) 289(26) 237(48)
GH 461(48)*** 162(16)*** 122(8)***
Serum insulin (µ-units/ml) Control 10(1) 14(1) 16(1)
GH 13(3) 22(4)*** 29(5)***
Serum C-peptide (pmol/ml) Control 0.26(0.05) 27(0.06) 0.29(0.07)
GH 0.47(0.04)** 0.41(0.04)** 0.51(0.06)***
Serum GH (m-units/l) Control 2.6(1.6) 4.2(1.7) 12.0(3.7)
GH 1.3(0.7) 5.1(2.4) 1.1(0.3)**
Plasma glucagon (pg/ml) Control 126(14) 90(9) 76(10)
GH 140(23) 112(28) 95(20)
Serum IGF-I (ng/ml) Control 191(7) 180(7) 173(6)
GH 376(46)*** 369(20)*** 354(24)***
Serum IGFBP-1 (ng/ml) Control 45(5) 39(3) 31(2)
GH 40(6) 34(4) 23(1)
Serum IGFBP-3 (mg/l) Control 3.2(0.2) 3.3(0.2) 3.3(0.2)
GH 5.9(0.4)*** 5.4(0.2)*** 5.2(0.3)***

Normoglycaemia was maintained during clamp measurements, with a mean intra-individual coefficient of variation for glucose of 6.5%. During clamps, insulin, C-peptide, IGF-I and IGFBP-3 levels were higher, while NEFA levels were lower, after treatment when compared with the control clamp. No change was found in clamp levels of blood glucose or IGFBP-1 after treatment when compared with the control clamp. Apart from the change in insulin levels (P<0.01) in response to glucose and insulin infusion, GH treatment did not affect the responses of substrates and hormones during glucose and insulin infusion when compared with basal levels ( Table 1).

Insulin sensitivity measurements and indirect calorimetry

Insulin infusion rates were required to be 40–50% higher in order to maintain normoglycaemia after GH treatment, and the M/I ratio decreased by 30–40% ( Table 2) compared with control conditions. The relative changes in the M/I ratio (M/I%) at high glucose infusion rates after treatment, measuring the change in insulin sensitivity, correlated with the change in basal levels of serum insulin (r = -0.86, P =0.03) and IGF-I (r =-0.85, P = 0.03) and the insulin/glucagon ratio (r =-0.92, P = 0.009). Energy expenditure increased after GH treatment (P < 0.05; Table 2), whereas no change was found in respiratory quotients or in glucose or fat oxidation rates.

Effects of GH treatment on insulin sensitivity and indirect calorimetry measurements in healthy volunteers

The subjects (n = 6) underwent a clamp study twice, before and after 5 days of daily single subcutaneous injections of GH (0.05mg·24h-1·kg-1). The clamp involved predetermined glucose infusion rates of 2 and 5mg·min-1·kg-1, with a variable infusion of insulin given in order to maintain normoglycaemia. Values are given as means (S.E.M.). Significance of differences: *P < 0.05, **P < 0.01, ***P < 0.001 compared with control, using two-way ANOVA for repeated measurements, and least significant difference as post hoc test. The respiratory quotients is calculated as (CO2 output)/(O2 consumption). Note that 1kcal = 4.184 kJ.
Glucose infusion
Parameter Basal 2mg·min-1·kg-1 5mg·min-1·kg-1
Insulin infusion rate (m-units·min-1·kg-1) Control 0(0) 0.15(0.003) 0.21(0.004)
GH 0(0) 0.25(0.002)* 0.36(0.004)**
M/I ratio Control 0(0) 0.15(0.01) 0.32(0.02)
GH 0(0) 0.10(0.02)* 0.21(0.04)***
Energy expenditure (kJ·24h-1·kg-1) Control 102.5(3.3) 102.5(3.8) 104.6(3.3)
GH 107.9(2.1)* 107.9(3.3)* 110.9(2.9)**
Respiratory quotient Control 0.82(0.02) 0.86(0.02) 0.92(0.02)
GH 0.82(0.02) 0.88(0.02) 0.94(0.02)
Glucose oxidation (mg·min-1·kg-1) Control 1.5(0.2) 1.9(0.2) 3.2(0.4)
GH 1.7(0.2) 2.5(0.2) 3.5(0.4)
Fat oxidation (mg·min-1·kg-1) Control 0.9(0.1) 0.7(0.1) 0.4(0.1)
GH 0.7(0.2) 0.6(0.1) 0.3(0.1)

Nitrogen balance, urinary nitrogen excretion, urinary 3-methylhistidine excretion and protein synthesis rates

There were no changes in 24h urinary nitrogen excretion, nitrogen balance or urinary 3-methylhistidine excretion during the 3-day sampling period before any study (P = 0.6). The mean levels of urinary nitrogen excretion for the 3-day sampling period were 26% lower after GH treatment (control, 12.9±0.8g of N/24h; GH, 9.6±1.0g/24h; P < 0.01). Similarly, a increase in nitrogen balance of 3.4g of N/24h was found after treatment (control, +1.3±0.6g/24h; GH, +4.7±0.7g/24h; P < 0.01). In contrast, no significant change was found in muscle protein synthesis rates in skeletal muscle after treatment (control, 1.92±0.20%/24h; GH, 2.13±0.16%/24h), and no change was found in urinary 3-methylhistidine excretion (control, 946±68µmol/24h; GH, 876±63µmol/24h).

Whole-body impedance measurements

GH treatment for 5 days resulted in slight but significant changes in body composition ( Table 3). Body fat was reduced, while lean body weight, lean/fat ratio and total body water increased after treatment (P < 0.05).

Effects of GH treatment on body composition

Changes in body composition were measured by whole-body impedance analysis in six healthy volunteers before (control) and after 5 days of single subcutaneous injections of GH (0.05mg·24h-1·kg-1). All values are given as mean (S.E.M.). Significance of differences: *P < 0.05 compared with control (Wilcoxon's signed rank test).
Parameter Control GH
Body water (%) 60.5(1.9) 61.8(1.6)*
Fat (%) 18.3(2.0) 16.3(1.5)*
Lean tissue (%) 81.7(2.0) 83.7(1.5)*
Lean/fat ratio 4.8(0.8) 5.4(0.7)*
Body weight (kg) 70.2(1.7) 71.0(1.8)

DISCUSSION

As anticipated, GH treatment reduced insulin sensitivity. However, when normalizing glucose flux with additional insulin, intracellular oxidation rates of glucose and fat were also normalized. The improved nitrogen economy after GH treatment seems to be due largely to an improved nitrogen balance in non-muscle tissues.

In the present study, we did not measure hepatic glucose production, and an increase in glucose production after GH treatment could possibly interfere with the interpretation of our results [ 9, 29]. However, several studies have shown that there is only a minimal, if any, change in glucose production after brief treatment with moderate doses of GH [ 3, 5, 30–32]. Healthy subjects given an infusion of GH after consumption of a standardized mixed meal displayed a similar decrease in hepatic glucose production postprandially as those given saline [ 31], possibly as a result of a compensatory increase in endogenous insulin secretion in the GH-treated subjects. Thus, since glucose flux was also normalized by compensatory hyperinsulinaemia in the present study, we believe that the contribution of glucose production to whole-body glucose disposal was not markedly different after GH treatment when compared with during the control period. Assuming that glucose production was unchanged by treatment, non-oxidative glucose disposal would also be unaffected by GH during glucose and insulin infusion, since glucose oxidation was unchanged and glucose infusion rates were the same after treatment.

The observed reduction in insulin sensitivity after treatment with GH in the present study was directly related to the increase in basal levels of serum IGF-I. This relationship may suggest that insulin resistance in response to GH treatment is induced to counteract the increased insulin-like activity contributed by IGF-I, in order to avoid side effects such as hypoglycaemia. This hypothesis remains to be tested in future studies. However, in postoperative patients with insulin resistance where insulin sensitivity is acutely reduced by surgery, insulin infusion increases levels of free IGF-I, via increased proteolytic activity directed against IGFBP-3 [ 33, 34]. In contrast, preliminary data have shown that, in a situation where insulin sensitivity was acutely increased, insulin infusion immediately after exercise was associated with a reduction in the levels of free IGF-I, through reduced proteolysis of IGFBP-3 and increased levels of IGFBP-1 [ 35]. Together, these data indicate that the effects of insulin and IGF-I are balanced in situations where insulin sensitivity is acutely increased or decreased, possibly to reduce the risk of systemic side effects such as hypoglycaemia.

Notably, the decreased insulin sensitivity after GH treatment was not related to a decreased insulin/glucagon ratio, which has been demonstrated in insulin-resistant states such as diabetes mellitus [ 36], starvation [ 36] and after burn trauma [ 37]. In contrast, a direct relationship was found between the decreased insulin sensitivity and an increased insulin/glucagon ratio. This suggests that mechanisms behind GH-induced insulin resistance differ from those reported in other conditions of insulin resistance.

GH promotes lipolysis directly by stimulating the activity of hormone-sensitive lipase. Administration of IGF-I has been shown both to inhibit [ 39] and to stimulate [ 40] lipolysis. The effects of IGF-I on lipolysis may be mediated directly by IGF-I through the insulin receptor, since virtually no IGF-I receptors are found in adipose tissue [ 41], or by modulation of serum insulin levels. Similar to what was found after 3 days of treatment with GH in rats [ 8], NEFA levels actually decreased in our subjects after treatment with GH. In addition, no change was found in fat oxidation rates after GH treatment. Altogether, these data do not support an involvement of the glucose/fatty acid cycle [ 42] in the development of insulin resistance after GH treatment. However, since increased lipolysis may be an early effect of GH treatment [ 8], contributions of the glucose/fatty acid cycle to the reduced insulin sensitivity in the early phase after GH administration, even in the present study, cannot be excluded.

There may be a difference between the direct and indirect (through IGF-I) effects of GH on protein metabolism. Effects of GH on protein metabolism after short-term infusions are probably due to GH directly, since IGF-I concentrations increase only after 6–12h [ 4]. Furthermore, when GH was infused in healthy subjects and IGF-I and insulin were maintained using an infusion of somatostatin, protein oxidation was decreased and protein synthesis in non-muscular tissues was increased, whereas no change was found in skeletal muscle protein synthesis [ 43]. In contrast, GH infused into the brachial artery for a longer period of time was shown to stimulate muscle protein synthesis, possibly due to paracrine production of IGF-I [ 4]. In addition, IGF-I given as an arterial infusion was shown to both increase protein synthesis and reduce proteolysis in skeletal muscle [ 44]. In the present study, no effect on skeletal muscle protein synthesis was found after treatment with GH, which is in accordance with some previous reports [ 43], but not others [ 4]. McNurlan et al. [ 45] demonstrated a 27% increase in protein synthesis rates in healthy subjects after 2 weeks of treatment with GH (6mg/day as daily subcutaneous injections), as compared with the non-significant 11% increase observed in the present study using a dose of 3–4mg/day (0.05mg·24h-1·kg-1). In the study of McNurlan et al. [45], the IGF-I response was more pronounced (4-fold) than in the present study (2-fold), due to the higher dose of GH given, while energy intake was similar (1.5×basal energy expenditure; 20% of energy from protein). Protein synthesis rates were measured in the present study with subjects in a 'pseudo-fed' state during insulin and glucose infusion, as glucose flux was maintained at the control level after GH treatment by compensatory hyperinsulinaemia. Thus protein synthesis rates may have been influenced not only by GH and IGF-I, but also by the prevailing insulin levels, which are the common conditions for 'daytime' metabolism. However, insulin infusion has repeatedly been reported not to stimulate protein synthesis rates in skeletal muscle when amino acids are not administered along with the insulin and glucose infusion [ 25, 46, 47], and may have little impact in the present study.

Similar to what has been reported previously [ 48], nitrogen excretion in urine was reduced after treatment with GH, indicating a decrease in whole-body protein oxidation [ 43] and urea synthesis [ 49]. Protein synthesis in skeletal muscle and urinary 3-methylhistidine excretion, a measure of muscle protein breakdown [ 10], were unchanged by GH treatment. Thus the present data suggest that the nitrogen-sparing effects of GH may be due largely to effects on protein synthesis and/or protein breakdown in tissues other than skeletal muscle (i.e. liver). This was not measured. However, the reduction in liver protein synthesis found in otherwise healthy subjects during laparoscopic cholecystectomy was shown to be prevented by 5 days' administration of GH (4mg/24h) [ 50], a dose similar to the one used in the present study.

The increases in energy expenditure, lean body mass and water retention, as well as the reduced fat content as measured by indirect calorimetry and whole-body impedance analysis, are in accordance with previous studies and have been discussed elsewhere [ 2, 51].

In summary, hyperinsulinaemia normalizes the glucose utilization rate, despite the presence of insulin resistance accompanying GH treatment, thereby normalizing intracellular oxidation rates of glucose and fat. Improved nitrogen economy after GH treatment seems to be due largely to an improved nitrogen balance in non-muscle tissues.

ACKNOWLEDGMENTS

We are grateful to Susan Anderson for skilful GC-MS analyses. The expert nursing assistance of Viveka Gustavsson and Lotta Hylén is also gratefully acknowledged. This work was supported by grants from the Karolinska Institute, the Nordic Insulin Foundation, the Swedish Medical Research Council (projects 09101, 4224 and 04210), the National Institutes of Health (grant 2RO1DK4931605A1), The Henning and Johan Throne Holst Foundation, The Maud and Birger Gustavsson Foundation, Nestec Ltd, Switzerland, and Kabi Pharmacia, Sweden.
REFERENCES

1 Brismar, K. and Hall, K. (1993) Clinical applications of IGFBP-1 and its regulation. Growth Regul. 3, 98–100
Medline 1st Citation

2 Bak, J. F., Møller, N. and Schitz, O. (1991) Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans. Am. J. Physiol. 260, E736–E742
Medline 1st Citation 2nd

3 Møller, N., Jørgensen, J. O. L., Alberti, K. G. M. M., Flyvbjerg, A. and Schmitz, O. (1990) Short-term effects of growth hormone on fuel oxidation and regional substrate metabolism in normal man. JPEN J. Parenter. Enteral Nutr. 70, 1179–1186
1st Citation 2nd

4 Fryburg, D. A., Louard, R. J., Gerow, K. E., Gelfand, R. A. and Barrett, E. J. (1991) Growth hormone stimulates skeletal muscle protein synthesis and antagonizes insulin's antiproteolytic action in humans. Diabetes 41, 424–429
1st Citation 2nd 3rd 4th

5 Horber, F. F., Marsh, H. M. and Haymond, M. W. (1991) Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans. Diabetes 40, 141–149
Medline 1st Citation 2nd

6 Douglas, R. G., Humberstone, D. A., Haystead, A. and Shaw, J. H. F. (1990) Metabolic effects of recombinant human growth hormone: isotopic studies in the postabsorbtive state and during total parenteral nutrition. Br. J. Surg. 77, 785–790
Medline 1st Citation

7 Copeland, K. C. and Nair, K. S. (1994) Recombinant human insulin-like growth factor-I increases forearm blood flow. J. Clin. Endocrinol. Metab. 79, 230–232
Medline 1st Citation

8 Hettiarachchi, M., Watkinson, A., Jenkins, A., Theos, V., Ho, K. and Kraegen, E. (1996) Growth hormone-induced insulin resistance and its relationship to lipid availability in the rat. Diabetes 45, 415–421
Medline 1st Citation 2nd 3rd

9 Rizza, R. A., Mandarino, L. J. and Gerich, J. E. (1982) Effects of growth hormone on insulin action in man. Diabetes 31, 663–667
Medline 1st Citation 2nd

10 Williamson, D. H., Farrell, R., Kerr, A. and Smith, R. (1977) Muscle-protein catabolism after injury in man, as measured by urinary excretion of 3-methylhistidine. Clin. Sci. Mol. Med. 52, 527–533
Medline 1st Citation 2nd

11 DeFronzo, R. A., Tobin, J. D. and Andres, R. (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am. J. Physiol. 237, E214–E223
Medline 1st Citation 2nd

12 Gutniak, M., Blomqvist, G., Widén, L., Hamberger, B. and Grill, V. (1990) D-(U-11-C) glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects. Am. J. Physiol. 258, E805–E812
Medline 1st Citation

13 Hugget, A. S. and Nixon, D. A. (1957) Use of glucose peroxidase and 0-dianisidin in determinations of blood and urinary glucose. Lancet ii, 368–370
1st Citation

14 Grill, V., Pigon, J., Hartling, S., Binder, C. and Efendic, S. (1990) Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high responders. Metab. Clin. Exp. 39, 251–258
Medline 1st Citation

15 Faloona, G. R. and Unger, R. H. (1974) Glucagon radioimmunoassay technique. In Methods of Hormone Radioimmunoassay. (Jaffe, B. M. and Behrman, H. E., eds.), vol. 1, pp. 317–330, Academic Press, New York
1st Citation

16 Bang, P., Eriksson, U., Sara, V., Wivall, I. L. and Hall, K. (1991) Comparison of acid gel filtration prior to IGF-1 and IGF-2 radioimmunoassay–improvement by the use of truncated IGF-1 as radioligand in the IGF-1 radioimmunoassay. Acta Endocrinol. 124, 620–629
Medline 1st Citation

17 Povoa, G., Roovete, A. and Hall, K. (1984) Cross reaction of serum somatomedin binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid. Acta Endocrinol. 107, 563–570
Medline 1st Citation

18 Baxter, R. and Martin, J. (1986) Radioimmunoassay of growth hormone-dependent insulin like growth factor binding protein in human plasma. J. Clin. Invest. 78, 1504–1512
Medline 1st Citation

19 Soini, E. and Kojola, H. (1983) Time-resolved fluorometer for lanthanide chelates–a new generation of nonisotopic immunoassays. Clin. Chem. 29, 65–68
Medline 1st Citation

20 Hallman, H. L., Farnebo, L. O., Hamberger, B. and Jonsson, G. (1978) A sensitive method for the determination of plasma catecholamines using liquid chromatography with electrochemical detection. Life Sci. 323, 1049–1052
1st Citation

21 Ho, R. J. (1970) Radiochemical assay of long chain fatty acids using 63-Ni as tracer. Anal. Biochem. 36, 105–113
Medline 1st Citation

22 Takala, J., Keinänen, O., Väisänen, P. and Kaari, A. (1989) Measurement of gas exchange in intensive care: Laboratory and clinical validation of a new device. Crit. Care Med. 17, 1041–1047
Medline 1st Citation

23 Frayn, K. N. (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. J. Appl. Physiol. 55, 628–634
Medline 1st Citation

24 Garlick, P., Wernerman, J. and McNurlan, M. (1989) Measurement of the rate of synthesis in muscle of postabsorptive young men by injection of a flooding dose of [1-13C]leucine. Clin. Sci. 77, 329–336
Medline 1st Citation 2nd

25 McNurlan, M. A., Essen, P., Thorell, A. et al. (1994) Response of protein synthesis in human skeletal muscle to insulin: an investigation with L-[2H5]phenylalanine. Am. J. Physiol. 267, E102–E108
Medline 1st Citation 2nd 3rd

26 Bergstrom, J. (1962) Muscle electrolytes in man. Scand. J. Clin. Lab. Invest. 168, (Suppl. 14), 11–13
1st Citation

27 Calder, A., Andersson, S., Grant, I., McNurlan, M. and Garlick, P. (1992) The determination of low d5-phenylalanine enrichment (0.002–000.09 atom percent excess), after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 6, 421–424
Medline 1st Citation 2nd

28 Lukaski, H. C., Johnson, P. E., Bolonchuk, W. W. and Lykken, G. I. (1985) Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am. J. Clin. Nutr. 41, 810–817
Medline 1st Citation

29 Karlander, S., Vranic, M. and Efendic, S. (1986) Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance. Diabetologia 29, 778–783
Medline 1st Citation

30 Busch-Sørensen, M., Holst, J. J. and Lyngsøe, J. (1991) Short time effects of growth hormone on glucose metabolism and insulin and glucagon secretion in normal man. J. Endocrinol. Invest. 14, 25–30
Medline 1st Citation

31 Butler, P., Kryshak, E. and Rizza, R. (1991) Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans. Am. J. Physiol. 260, E513–E520
Medline 1st Citation 2nd

32 Neely, R. D. G., Rooney, D. P., Bell, N. P., Sheridan, B., Atkinson, A. B. and Trimble, E. R. (1992) Influence of growth hormone on glucose/glucose 6-phosphate cycle and insulin action in normal humans. Am. J. Physiol. 263, E980–E987
Medline 1st Citation

33 Bang, P., Nygren, J., Carlsson-Skwirut, C., Thorell, A. and Ljungqvist, O. (1998) Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity. J. Clin. Endocrinol. Metab. 83, 2509–2515
Medline 1st Citation

34 Nygren, J., Skwirut, C., Brismar, K., Thorell, A., Ljungqvist, O. and Bang, P. (2001) Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery. Am. J. Physiol. 281, E736–E741
1st Citation

35 Thorell, A., Skwirut, C., Ljungqvist, O., Bang, P. and Nygren, J. (2000) IGF-I bioavailability in response to insulin is altered after exercise. Clin. Nutr. 19, P50
1st Citation

36 Unger, R. H. and Dallas, M. D. (1972) Glucagon and the insulin-glucagon ratio in diabetes and other catabolic illnesses. Diabetes 20, 834–838
1st Citation 2nd

37 Nygren, J., Sammann, M., Malm, M. et al. (1995) Disturbed anabolic hormonal patterns in burned patients: the relation to glucagon. Clin. Endocrinol. 43, 491–500
1st Citation

38 Reference deleted

39 Laager, R., Ninnis, R. and Keller, U. (1995) Comparative effects of recombinant human insulin-like growth factor I and insulin on whole-body and forearm palmitate metabolism in man. Clin. Sci. 88, 681–686
Medline 1st Citation

40 Hussain, M., Schmitz, O., Mengel, A., Glatz, Y. and Christiansen, J. (1994) Comparison of the effects of growth hormone and insulin-like growth factor-I on substrate oxidation and on insulin sensitivity. J. Clin. Invest. 94, 1126–1133
Medline 1st Citation

41 Zapf, J., Schoenle, E. and Waldvogel, M. (1981) Effect of trypsin treatment of rat adipocytes on biological effects and binding of insulin and insulin-like growth factors. Eur. J. Biochem. 113, 605–609
Medline 1st Citation

42 Randle, P. J., Kerbey, A. L. and Espinal, J. (1988) Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diabetes Metab. Rev. 4, 623–638
Medline 1st Citation

43 Copeland, K. C. and Nair, K. S. (1994) Acute growth hormone effects on amino acid and lipid metabolism. J. Clin. Endocrinol. Metab. 78, 1040–1047
Medline 1st Citation 2nd 3rd

44 Fryburg, D. (1994) Insulin-like growth factor-I exerts growth hormone- and insulin-like actions on human muscle protein metabolism. Am. J. Physiol. 267, E331–E336
Medline 1st Citation

45 McNurlan, M., Garlick, P., Steigbigel, R. et al. (1997) Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J. Clin. Invest. 100, 2125–2132
Medline 1st Citation

46 Nair, K. S., Ford, G. C., Ekberg, K., Fernqvist-Forbes, E. and Wahren, J. (1995) Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. J. Clin. Invest. 95, 2926–2937
Medline 1st Citation

47 Meek, S. E., Persson, M., Ford, G. C. and Nair, K. S. (1998) Differential regulation of amino acid exchange and protein dynamics across splanchnic and skeletal muscle beds by insulin in healthy human subjects. Diabetes 47, 1824–1835
Medline 1st Citation

48 Kupfer, S., Underwood, L., Baxter, R. and Clemmons, D. (1993) Enhancement of the anabolic effects of growth hormone and insulin-like growth factor-I by use of both agents simultaneously. J. Clin. Invest. 91, 391–396
Medline 1st Citation

49 Grofte, T., Wolthers, T., Jensen, S. et al. (1997) Effects of growth hormone and insulin-like growth factor-I singly and in combination on in vivo capacity of urea synthesis, gene expression of urea cycle enzymes, and nitrogen contents in rats. Hepatology 25, 964–969
Medline 1st Citation

50 Barle, H., Essen, P., Nyberg, B. et al. (1999) Depression of liver protein synthesis during surgery is prevented by growth hormone. Am. J. Physiol. 276, E620–E627
Medline 1st Citation

51 Wolfe, R. F., Heslin, M. J., Newman, E., Pearlstone, D. B., Gonenne, A. and Brennan, M. F. (1992) Growth hormone and insulin combine to improve whole-body and skeletal muscle protein kinetics. Surgery 12, 284–292
1st Citation




Thank you, have a nice day

 

[goldylight]

now look what you made bobo do:goodpost:

 

[DrBobbo]

now look what you made bobo do:goodpost:

yeah seriously, instead of posting all that how about suggesting something
about my diet guys? Bobo? :blink:

 

[goldylight]

well if i were in college, i would figure out what not to eat. then stuff my face as often as i could with the good stuff.

 

[taffer]

wow that big post is very confusing for anyone without a PhD
from what i gather its basically saying protein is more important around your workout(better resynthasis...i think), and errr, GH is good or something

heh im probly wrong, but i can hardly get my head around most of that stuff!

 

[LunaHotel]

What you are writing does not contradict what I wrote, but I express my thanks for the informative consideration.

 

[Dwight Schrute]

What you are writing does not contradict what I wrote, but I express my thanks for the informative consideration.

If you don't get it after that, you never will. Its funny everyone seemed to get it. Wonder why you didn't?

 

[Dwight Schrute]

I don't know which specific things of these you don't know, but do read up, please.

Look in the mirror.


Next time you want to get into an "informative" discussion, please know what you are talking about before you say I am wrong, or say anything for that matter.

 

[bulkmuscle]

chocolate whey + lemon lime gatorade = lemon marangue pie

mmmm

 

[kraftkid]

Damn. I just got to this post. Bobo just invented a new condition, "intellectual roid rage". If I ever piss you off, I'm sorry!!!

 

[Grassroots082]

Just wanted to bump this thread, I love reading Bobo's old posts. Oatmeal before and after and never better

 

[Gutterpump]

haha I'll eat / drink anything for gains. I used to drink egg beaters for breakfast until I got sick of them.

lol I do the same from time to time...egg beaters right out of the carton...any time of the day.

It's true about sugar after your workouts though...you don't really need to trigger an insulin response as your body is already going to suck up the protein like it's nothing. Oatmeal is enough to replenish your glycogen stores.

The only time I personally intake dextrose is with my creatine, but it's already included in my greenMAG / Torrent (although again I question if a high-gi carb is needed in torrent for post-workout). Always thought that was a bit trivial.