The effects of BCAAs intake on insulin

[JudoJosh]

Effects of branched-chain amino acid supplementation on plasma concentrations of free amino acids, insulin, and energy substrates in young men.

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.

PMID 21512300

 

[JudoJosh]

Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulin.

Feeding stimulates pancreatic digestive enzyme synthesis at the translational level, and this is thought to be mediated by hormones and neurotransmitters. However, BCAAs, particularly leucine, stimulate protein synthesis in several tissues. We investigated whether BCAA stimulated the translational machinery in murine pancreas and whether their effects were independent of hormones. Rats and mice were administered (i.g. gavage) individual BCAA at 1.35 mg/g (body weight) and rat isolated pancreatic acini were incubated with BCAA under different conditions. Activation of translation initiation factors and total protein synthesis were analyzed. BCAA gavage stimulated the phosphorylation of the initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and the ribosomal protein S6 kinase (S6K), with leucine being the most effective. Leucine also increased the association of the initiation factors eIF4E and eIF4G, but did not affect the activity of the guanine nucleotide exchange factor eIF2B, nor total protein synthesis. BCAA acted independently of insulin signaling on isolated pancreatic acini from diabetic rats. The ability of leucine to promote phosphorylation of 4E-BP1 and S6K as well as enhance the assembly of the eIF4F complex was unimpaired in CCK-deficient mice. Finally, rapamycin (0.75 mg/kg) administered to rats 2 h before leucine gavage inhibited the phosphorylation of S6 and 4E-BP1 induced by leucine. We conclude that leucine may participate, as a signal as well as a substrate, in activating the translational machinery in pancreatic acinar cells independently of hormonal effects and that this action is through the mTOR pathway.

Another one on leucine

Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome

Abstract

Diets with total protein intake >1.5 g·kg−1·d−1 and carbohydrate intake <150 g/d are effective for treatment of obesity, type 2 diabetes, and the Metabolic Syndrome. These diets improve body composition and enhance glycemic control. During weight loss, protein-rich diets reduce loss of lean tissue and increase loss of body fat. Specific mechanisms to explain each of these clinical outcomes remain to be fully elucidated. We propose that keys to understanding the relationship between dietary protein and carbohydrates are the relationships between the branched-chain amino acid leucine and insulin and glucose metabolism. Leucine is known to interact with the insulin signaling pathway to stimulate downstream signal control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Leucine also appears to modulate insulin signaling and glucose use by skeletal muscle. Whereas total protein is important in providing substrates for gluconeogenesis, leucine appears to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle. These mechanisms produce protein sparing and provide a stable glucose environment with low insulin responses during energy-restricted periods.

 

[JudoJosh]

direct effects of leucine on insulin release from the pancreas

Leucine signaling in the pathogenesis of type 2 diabetes and obesity.

Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.

 

[criticalbench]

Good posts man. Really enjoying reading these!

 

[CJ_Xfit89]

In.sum????

 

[mr.cooper69]

In.sum????

Before you can answer "what?" you must first understood "how?"

 

[CJ_Xfit89]

Before you can answer "what?" you must first understood "how?"

Teach.me

 

[DaveGabe24]

Thank you very much Josh, I forget which forum, but I was just reading the other day that someone was talking about how they had less than stellar results with Layne because they felt his amino acid protocol was spiking their insulin too much.

Since then I had questioned the translational effectiveness of his refractory period theory, etc...but if there is no direct impact on glucose I cannot see the insulin response to AA's as a viable rebuttal to what Layne proposes.

 

[Blergs]

great post

 

[rambofireball]

According the the finding of the third posted study, leucine supplementation has a pro-diabetic affect by up-regulating MTORC1 and I guess therefore increasing insulin secretion and fat/muscle growth (the diabetic aspect being fat related). This is really interesting, as most of the lean gains/intermittent fasting protocols I've seen have promoted leucine use through fasting periods for fat-loss and muscle retention. I have personally had pretty unexciting results with LG/IF style diets when I've played with them. I actually felt that the intended fat-loss was being slowed down somehow regardless of my dialed training and diet, based on previous cutting phases. That being said, I've been experimenting with carb-backloading for the past month and have for the first time, in a couple years of serious training, been able to successfully start recomping. I believe the CBL style diet argues that leucine should only be used post-training or at least around the time of training (pre-intra-post) for the exact reasons displayed in the above studies. Interesting stuff, thanks for posting.