Matt hits the books to come up with gold:
J Microbiol Biotechnol. 2012 Jan;22(1):147-55.
Synergic effects of bitter melon and β-Glucan composition on STZ-induced rat diabetes and its complications.
Kim JW, Cho HR, Moon SB, Kim KY, Ku S.
Glucan Corp. Research Institute, Marine Biotechnology Center, Busan 617-763, Korea.
β-Glucan purified from oats (OG) and bitter melon, Momordica charantia Linn (MC), water extracts have shown favorable effects on diabetes and its complications. We investigated to find out the optimal composition showing hypoglycemic and antidiabetic complication effects in variable compositions (OG:MC = 1:1, 1:2, 1:4, 1:6, 1:8, 1:10, 2:1, 4:1, 6:1, 8:1, 10:1). Extracts were administered orally once a day for 28 days following 7 days post streptozotocin (STZ) dosing. Five rats per group (total 15 groups; Intact, STZ, OG, MC, and the variable composition groups) were selected according to the blood glucose and body weight at 6 days after STZ dosing. After 28 days of extracts dosing, the changes on the body weight, liver and kidney weight, blood glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), low-density lipoprotein (LDL), and total-cholesterol levels were observed. As the result of STZ-induced diabetes, decreases of body weight, increases of the liver and kidney weights, blood glucose, BUN, creatinine, AST, ALT, LDL, and total-cholesterol levels in STZ control were detected compared with intact control. However, these changes of hyperglycemia, diabetic nephropathy, hepatopathy, and hyperlipemia were dramatically decreased in the OG and MC single-dosing group, and all composition groups. In addition, there were more favorable effects in all composition groups compared with the OG and MC single-dosing groups. Among variable compositions, the OG:MC 1:2 mixed group showed the most synergic effects in this study.
PMID:22297232 [PubMed - indexed for MEDLINE]
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Bitter melon extracts in diabetic and normal rats favorably influence blood glucose and blood pressure regulation.
Clouatre DL, Rao SN, Preuss HG.
Glykon Technologies Group, LLC, Santa Monica, California, USA. email@example.com
Bitter melon (BM) was tested in normal and streptozotocin (STZ)-induced diabetic rats. First, normal and diabetic Wistar rats were given four test extracts (EX-1-EX-4) of a wild-genotype BM or metformin by intubation. Second, normal Sprague-Dawley rats were divided into control and three test groups given for 52 days one of three BM preparations in food: Chinese or Indian commercial preparations or EX-4 from experiment I. In experiment I, extracts of BM administered at 50 mg/kg of body weight in normal rats reduced blood sugar for 4 hours without, unlike metformin, inducing hypoglycemia. In STZ-induced diabetic rats, two extracts administered at 250 mg/kg decreased glucose levels to values comparable to metformin at 150 mg/kg. At 4 hours, EX-1 and EX-4 significantly reduced blood glucose 67% and 63%, respectively, compared with metformin's 54%. In experiment II, all test groups had lowered systolic, but not diastolic, blood pressure. The China and EX-4 arms had significantly lowered serum glucose levels compared with the control. In the glucose tolerance test, only EX-4 had significantly lowered glucose levels. Only EX-4 had significantly lowered angiotensin converting enzyme (ACE) activity. All active arms showed significance in the losartan challenge (the renin-angiotensin system [RAS]), with the greatest effect in the EX-4 group. In the N(ω)-nitro-l-arginine-methyl ester challenge, only EX-4 exhibited a significant impact on the nitric oxide system, suggesting higher activity in this group. In the STZ-induced diabetic rat model, wild-type BM powerfully lowered glucose levels, and, in healthy adult rats, wild-type BM exhibited beneficial effects in the regulation of blood glucose, in RAS and ACE inhibition, and in nitric oxide generation.
The combination of our special extract and the Norvaline will have a potent effect on NO generation and vascular dilation.J Nutr Biochem. 2011 Nov;22(11):1064-73. Epub 2011 Jan 28.
Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice.
Wang ZQ, Zhang XH, Yu Y, Poulev A, Ribnicky D, Floyd ZE, Cefalu WT.
Center for the Study of Botanicals and Metabolic Syndrome, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA 70808, USA. wangzq@PBRC.edu
Bioactive components from bitter melon (BM) have been reported to improve glucose metabolism in vivo, but definitive studies on efficacy and mechanism of action are lacking. We sought to investigate the effects of BM bioactives on body weight, muscle lipid content and insulin signaling in mice fed a high-fat diet and on insulin signaling in L6 myotubes. Male C57BL/6J mice were randomly divided into low-fat diet control (LFD), high-fat diet (HFD) and HFD plus BM (BM) groups. Body weight, body composition, plasma glucose, leptin, insulin and muscle lipid profile were determined over 12 weeks. Insulin signaling was determined in the mouse muscle taken at end of study and in L6 myotubes exposed to the extract. Body weight, plasma glucose, insulin, leptin levels and HOMA-IR values were significantly lower in the BM-fed HFD group when compared to the HFD group. BM supplementation significantly increased IRS-2, IR β, PI 3K and GLUT4 protein abundance in skeletal muscle, as well as phosphorylation of IRS-1, Akt1 and Akt2 when compared with HFD (P<.05 and P<.01). BM also significantly reduced muscle lipid content in the HFD mice. BM extract greatly increased glucose uptake and enhanced insulin signaling in L6 myotubes. This study shows that BM bioactives reduced body weight, improved glucose metabolism and enhanced skeletal muscle insulin signaling. A contributing mechanism to the enhanced insulin signaling may be associated with the reduction in skeletal muscle lipid content. Nutritional supplementation with this extract, if validated for human studies, may offer an adjunctive therapy for diabetes.
Copyright © 2011 Elsevier Inc. All rights reserved.
Eur J Nutr. 2012 May 19. [Epub ahead of print]
4-Hydroxyisoleucine stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells via phosphatidylinositol-3-kinase-dependent pathway.
Jaiswal N, Maurya CK, Venkateswarlu K, Sukanya P, Srivastava AK, Narender T, Tamrakar AK.
Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, 226001, India.
To determine the effect of 4-Hydroxyisoleucine (4-HIL), an unusual amino acid isolated from the seeds of Trigonella foenum-graecum, on glucose uptake and the translocation of glucose transporter 4 (GLUT4) to plasma membrane in skeletal muscle cells and to investigate the underlying mechanisms of action.
Rat skeletal muscle cells (L6-GLUT4myc) were treated with 4-HIL, and the effect on glucose uptake was determined by measuring the incorporation of radio-labeled 2-deoxy-[(3)H]-D: -glucose (2-DG) into the cell. Translocation of GLUT4myc to plasma membrane was measured by an antibody-coupled colorimetric assay.
The prolonged exposure (16 h) of L6-GLUT4myc myotubes to 4-HIL caused a substantial increase in the 2-DG uptake and GLUT4 translocation to the cell surface, without changing the total amount of GLUT4 and GLUT1. Cycloheximide treatment reversed the effect of 4-HIL on GLUT4 translocation to the basal level suggesting the requirement of new protein synthesis. The 4-HIL-induced increase in GLUT4 translocation was completely abolished by wortmannin, and 4-HIL significantly increased the basal phosphorylation of AKT (Ser-473), but did not change the mRNA expression of AKT, IRS-1, GLUT4, and GSK3β.
Results suggest that 4-HIL stimulates glucose uptake in L6-GLUT4myc myotubes by enhancing translocation of GLUT4 to the cell surface in a PI-3-kinase/AKT-dependent mechanism.
PMID:22610671 [PubMed - as supplied by publisher]
Adipocyte-Derived Th2 Cytokines and Myeloid PPARδ Regulate Macrophage Polarization and Insulin Sensitivity
Kihwa Kang1, Shannon M. Reilly1, Volkan Karabacak1, Matthew R. Gangl1, Kelly Fitzgerald1, Ben Hatano1, 2 and Chih-Hao Lee1, ,
1 Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, MA 02115, USA
2 Present address: Department of Pathology, Japan Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Tokyo 154-0001, Japan
The polarization of adipose tissue-resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to improve insulin sensitivity. However, the mechanisms controlling tissue macrophage activation remain unclear. Here we show that adipocytes are a source of Th2 cytokines, including IL-13 and to a lesser extent IL-4, which induce macrophage PPARδ/β (Ppard/b) expression through a STAT6 binding site on its promoter to activate alternative activation. Coculture studies indicate that Ppard ablation renders macrophages incapable of transition to the M2 phenotype, which in turns causes inflammation and metabolic derangement in adipocytes. Remarkably, a similar regulatory mechanism by hepatocyte-derived Th2 cytokines and macrophage PPARδ is found to control hepatic lipid metabolism. The physiological relevance of this paracrine pathway is demonstrated in myeloid-specific PPARδ−/− mice, which develop insulin resistance and show increased adipocyte lipolysis and severe hepatosteatosis. These findings provide a molecular basis to modulate tissue-resident macrophage activation and insulin sensitivity.
The addition of fenugreek extract (Trigonella foenum-graecum) to glucose feeding increases muscle glycogen resynthesis after exercise.
Ruby BC, Gaskill SE, Slivka D, Harger SG.
Department of Health and Human Performance, The University of Montana, Missoula, Montana 59812-1825, USA. firstname.lastname@example.org
The purpose of this study was to determine the effects of ingesting an oral supplement containing 4-Hydroxyisoleucine (4-OH-Ile, isolated from fenugreek seeds [Trigonella foenum-graecum]) with a glucose beverage on rates of post-exercise muscle glycogen resynthesis in trained male cyclists. Following an overnight fast (12 hr), subjects completed a 90-minute glycogen depletion ride after which a muscle biopsy was obtained from the vastus lateralis. Immediately and 2 hours after the muscle biopsy, subjects ingested either an oral dose of dextrose (Glu) (1.8 g.kg BW(-1)) or 4-OH-Ile supplement (Glu+4-OH-Ile, including 2.0 mg.kg(-1) 4-OH-Ile with the same oral dose of dextrose) with a second muscle biopsy 4 hours after exercise. Post exercise muscle glycogen concentration was similar for both trials. Overall, there was a significant increase in glucose and insulin concentrations from time 0 throughout the majority of the 4-hour recovery period, with no significant differences between the two trials at any time point. Although muscle glycogen concentration significantly increased from immediately post exercise to 4 hr of recovery for both trials, the net rate of muscle glycogen resynthesis was 63% greater during Glu+4-OH-Ile (10.6+/-3.3 vs. 6.5+/-2.6 g.kg wet wt.(-1).hr.(-1) for the Glu+4-OH-Ile and Glu trials, respectively). These data demonstrate that when the fenugreek extract supplement (4-OH-Ile) is added to a high oral dose of dextrose, rates of post-exercise glycogen resynthesis are enhanced above dextrose alone.
PMID:15719265 [PubMed - indexed for MEDLINE]
Activating effect of momordin, extract of bitter melon (Momordica Charantia L.), on the promoter of human PPARdelta.
Sasa M, Inoue I, Shinoda Y, Takahashi S, Seo M, Komoda T, Awata T, Katayama S.
Department of Diabetes and Endocrinology, Saitama Medical University, Japan.
Bitter melon (Momordica charantia L.) is a common vegetable grown in Okinawa that has also been used recently in medicine for the treatment of diseases such as diabetes, hypertension, and dyslipidemia. Among Bitter melon extracts compounds, we focused on an extract known as momordin in the present study, to examine its effect on peroxisome-proliferator activated-receptor (PPAR) delta (also called PPARdelta in rodents) expression and promoter activity of the human PPARdelta gene.
A human PPARdelta promoter-reporter plasmid was made as a template from a BAC CLONE (RPCI-11C) containing a -3076 bp (BglI site) +74 bp (EcoRI site) sequence. Luciferase assay of PPARdelta promoter activity was performed using HepG2 cells.
10 and 25 nM Momordin significantly increased the expression of PPARdelta mRNA 1.5-fold (relative to the control). Moreover, 10 and 25 nM Momordin significantly increased PPARdelta promoter activity in a dose-dependent manner, reaching more than 1.5-fold relative to the control.
Our present data obtained through successful cloning of the PPARdelta promoter demonstrate that PPARdelta production and activation are upregulated through PPARdelta promoter activity following momordin treatment.
PMID:20032574 [PubMed - indexed for MEDLINE]and this...Tannic acid stimulates glucose transport and inhibits adipocyte differentiation in 3T3-L1 cells.
Liu X, Kim JK, Li Y, Li J, Liu F, Chen X.
Department of Biochemistry, Edison Biotechnology Institute, College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Obesity is a major risk factor for Syndrome X and type II diabetes (T2D). However, most antidiabetic drugs that are hypoglycemic also promote weight gain, thus alleviating one symptom of T2D while aggravating a major risk factor that leads to T2D. Adipogenesis, the differentiation and proliferation of adipocytes, is a major mechanism leading to weight gain and obesity. It is highly desirable to develop pharmaceuticals and treatments for T2D that reduce blood glucose levels without inducing adipogenesis in patients. Previously, we reported that an extract from Lagerstroemia speciosa L. (banaba) possessed activities that both stimulated glucose transport and inhibited adipocyte differentiation in 3T3-L1 cells. Using glucose uptake assays and Western/Northern blot analyses as major tools and 3T3-L1 cells as a model, we showed that the banaba extract (BE) with tannin removed was devoid of the 2 activities, and tannic acid (TA), a major component of tannins, had the same 2 activities as BE. Inhibitors known to abolish insulin-induced glucose transport also blocked TA-induced glucose transport. We further detected that TA induced phosphorylation of the insulin receptor (IR) and Akt, as well as translocation of glucose transporter 4 (GLUT 4), the protein factors involved in the signaling pathway of insulin-mediated glucose transport. We also demonstrated that TA inhibited the expression of key genes for adipogenesis. Differences between samples with or without TA in all of the quantitative assays were significant (P < 0.05). These results suggest that TA may be useful for the prevention and treatment of T2D and its associated obesity. TA may have the potential to become the lead compound in the development of new types of antidiabetic pharmaceuticals that are able to reduce blood glucose levels without increasing adiposity
Get your GlycoMyx on!
Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa.
Klein G, Kim J, Himmeldirk K, Cao Y, Chen X.
College of Osteopathic Medicine, Edison Biotechnology Institute, Department of Chemistry and Biochemistry, The Molecular and Cellular Biology Program, Department of Biological Science and Department of Biomedical Science, Ohio University, USA.
The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG
It's not all about the Corosolic Acid.
What would be a good source of carbs to take with Slintensity, you ask? What about Zoidberg?
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2011 Jul;40(4):374-9.
[Effect of purple sweet potato flavonoids on metabolism of glucose and lipids in diabetic rats].
[Article in Chinese]
Jiang HF, Li XR, Tang C.
School of Medicine and Life Sciences, Zhejiang University City College, Hangzhou 310015, China.
To investigate the effects of purple sweet potato flavonoids (PSPF) on blood glucose and lipids levels in diabetic rats.
Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg.kg(-1)) in rats. The changes of fasting blood glucose and lipids levels in serum and body weight, food and fluid intake of diabetic rats treated with PSPF were examined.
Diabetic symptoms were ameliorated after rats were fed with PSPF. The fasting blood glucose (FBG), GSP, TC, TG, LDL-C were decreased and serum HDL-C levels were increased (P<0.01) in high, medium dose PSPF groups; while FBG, serum GSP, TG, LDL-C were also improved in low dose group (P<0.05 or P<0.01).
Purple sweet potato flavonoids can decrease the blood glucose and lipids levels in diabetic rats.
PMID:21845749 [PubMed - indexed for MEDLINE]