X-Message-Number: 32567 Date: Fri, 23 Apr 2010 19:07:16 -0700 (PDT) From: Subject: probable life extension with alpha-glucosidase inhibitors [Alpha-glucosidase inhibitors can lower glucose, insulin, body weight, and cholesterol levels. One such inhibitor (voglibose,) has even been shown to reverse atherosclerosis in humans. Sources of dietary inhibitors include adzuki bean, and white kidney bean.] Diabetes Res Clin Pract. 2005 Mar;67(3):204-10. alpha-Glucosidase inhibitor reduces the progression of carotid intima-media thickness. Yamasaki Y, Katakami N, Hayaishi-Okano R, Matsuhisa M, Kajimoto Y, Kosugi K, Hatano M, Hori M. Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan. Abstract OBJECTIVE: An open randomized prospective study was performed to elucidate the effect of an alpha-glucosidase inhibitor, voglibose, on the progression of atherosclerosis in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Voglibose at a dose of 0.4-0.6 mg/day was added on 51 subjects out of 101 type 2 diabetic patients being treated with diet, sulphonylurea (SU) or insulin injections, and the average (AveIMT) and maximum intima-media thickness (MaxIMT) of their carotid arteries were examined for 3 years. RESULTS: Irrespective of the differences in treatments, addition of voglibose reduced the progression of AveIMT and MaxIMT to -0.024 +/- 0.047 (+/-S.D.) and -0.021 +/- 0.144 mm/year, respectively. Without voglibose, diabetic patients showed significant (P < 0.0001) progression of AveIMT and MaxIMT (0.056 +/- 0.046 and 0.098 +/- 0.122 mm/year, respectively). The administration of voglibose resulted in a significant reduction of hemoglobin A1c (HbA1c), total cholesterol and triglyceride concentrations, as well as an increase in HDL cholesterol concentration. Multivariate regression analysis showed that administration of voglibose independently reduced the progression of AveIMT by 0.069 mm/year (P < 0.0001). CONCLUSIONS: These results suggest that voglibose reduces the progression of IMT and may be a candidate for an anti-atherosclerotic drug for type 2 diabetic patients. PMID: 15713352 Biochem Biophys Res Commun. 2007 Jul 6;358(3):679-85. Epub 2007 May 4. Swings in blood glucose levels accelerate atherogenesis in apolipoprotein E-deficient mice. Mita T, Otsuka A, Azuma K, Uchida T, Ogihara T, Fujitani Y, Hirose T, Mitsumata M, Kawamori R, Watada H. Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Abstract The aim of this study was to investigate the effect of fluctuations in blood glucose levels on atherogenesis. Apolipoprotein (apo) E-deficient mice fed maltose twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the number of macrophages adherent to the endothelium and the area of fibrotic arteriosclerotic lesions, with and without administration of miglitol, an alpha-glucosidase inhibitor. Macrophage adhesion to endothelial cells in thoracic aorta was quantitated by the en face method for optimal observation of endothelial surface after immunohistochemical staining for Mac-2. The area of arteriosclerotic lesions was measured in elastica van Giesson-stained proximal aorta. The number of adherent macrophages increased at 1 week after commencement of maltose feeding and the size of arteriosclerotic lesion increased at 5 weeks after such feeding. These increases were prevented by simultaneous use of miglitol. Our data demonstrated that glucose fluctuations accelerate atherogenesis. This was independent of changes in serum cholesterol level in vivo. Reduction of glucose fluctuation by alpha-glucosidase inhibitor efficiently controlled the progression of atherosclerosis. PMID: 17506980 [Adzuki bean lowers glucose and insulin in both diabetic and normal rodents.] Nutrition. 2009 Feb;25(2):134-41. Epub 2008 Oct 16. Hypoglycemic effect of hot-water extract of adzuki (Vigna angularis) in spontaneously diabetic KK-A(y) mice. Itoh T, Kobayashi M, Horio F, Furuichi Y. Department of Bio-Active Substances Research, Gifu International Institute of Biotechnology, Gifu, Japan. Abstract OBJECTIVE: Recently, we reported that 40% ethanol fraction of hot-water extracts of adzuki (Vigna angularis; EtEx.40) suppressed the postprandial blood glucose level and serum insulin level in normal mice and streptozotocin-induced type 1 diabetic rats. The present study examined the hypoglycemic effect of EtEx.40 on blood glucose, insulin concentrations, organ weight, serum composition, and hepatic lipid content in spontaneously diabetic KK-A(y)/Ta Jcl mice, a model for type 2 diabetes. METHODS: To investigate the prevention of type 2 diabetes by EtEx.40 ingestion, 4-wk-old non-diabetic KK-A(y) mice were fed an AIN-76 diet containing 5000 mg of EtEx.40/kg of body weight per day (EtEx.40) or an AIN-76 diet without EtEx.40 for 8 wk. Furthermore, to investigate the improvement of type 2 diabetes, 7-wk-old diabetic KK-A(y) mice were fed EtEx.40 for 4 wk. RESULTS: Compared with the control group, EtEx.40 supplementation had a significant effect in lowering blood glucose levels, water intake, serum insulin levels, urinary glucose, urinary microalbumin/creatinine ratio, liver triacylglycerol, and total cholesterol levels. Similar results were observed in 7-wk-old diabetic KK-A(y) mice fed EtEx.40 for 4 wk. These effects were also found after short-term administration of EtEx40. Overall, EtEx.40 improved several diabetic symptoms in KK-A(y) mice. CONCLUSION: EtEx.40 obtained from hot-water adzuki extracts showed preventive and ameliorative effects on the progression of diabetes in genetically diabetic KK-A(y) mice. In the present study, we conclude that the preventive and ameliorative effects by EtEx.40 were due to the modulation of blood glucose levels and the protective effect against oxidative damage in diabetes mellitus. PMID: 18929464 Biosci Biotechnol Biochem. 2004 Dec;68(12):2421-6. Suppressive effect of a hot water extract of adzuki beans (Vigna angularis) on hyperglycemia after sucrose loading in mice and diabetic rats. Itoh T, Kita N, Kurokawa Y, Kobayashi M, Horio F, Furuichi Y. Imuraya Confectionary Co. Ltd., Takachaya 7-1-1, Tsu, Mie 514-8530, Japan. Abstract A hot water extract obtained by boiling adzuki beans (Vigna angularis) to produce bean paste for Japanese cake showed inhibitory activity against alpha-glucosidase, alpha-amylase, maltase, sucrase, and isomaltase after HP-20 column chromatography. The IC(50) values for each hydrolylase were 0.78 mg/ml (alpha-amylase), 2.45 mg/ml (maltase), 5.37 mg/ml (sucrase), and 1.75 mg/ml (isomaltase). The active fraction showed potential hypoglycemic activity in both normal mice and streptozotocin (STZ)-induced diabetic rats after an oral administration of sucrose, but did not show any effect on the blood glucose concentration after glucose administration, suggesting that the active fraction suppressed the postprandial blood glucose level by inhibiting alpha-glucosidase and alpha-amylase, irrespective of the endogenous blood insulin level. PMID: 15618610 Fre text> http://www.jstage.jst.go.jp/article/bbb/68/12/2421/_pdf [White kidney bean lowers glucose and insulin in both diabetic and normal rodents. It is also effective for weight loss in humans.] Int J Med Sci. 2007 Jan 24;4(1):45-52. A Dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. Celleno L, Tolaini MV, D'Amore A, Perricone NV, Preuss HG. Cosmetic Research Center, dell'Universita Cattolica di Roma, Rome, Italy. Abstract BACKGROUND: More than one billion human adults worldwide are overweight and, therefore, are at higher risk of developing cardiovascular diseases, diabetes, and a variety of other chronic perturbations. Many believe that use of natural dietary supplements could aid in the struggle against obesity. So-called "starch blockers" are listed among natural weight loss supplements. Theoretically, they may promote weight loss by interfering with the breakdown of complex carbohydrates thereby reducing, or at least slowing, the digestive availability of carbohydrate-derived calories and/or by providing resistant starches to the lower gastrointestinal tract. AIMS: The present research study examines a dietary supplement containing 445 mg of Phaseolus vulgaris extract derived from the white kidney bean, previously shown to inhibit the activity of the digestive enzyme alpha amylase, on body composition of overweight human subjects. METHODS: A randomized, double-blinded, placebo-controlled study was conducted on 60 pre-selected, slightly overweight volunteers, whose weight had been essentially stable for at least six months. The volunteers were divided into two groups, homogeneous for age, gender, and body weight. The test product containing Phaseolus vulgaris extract and the placebo were taken one tablet per day for 30 consecutive days before a main meal rich in carbohydrates. Each subject's body weight, fat and non-fat mass, skin fold thickness, and waist/hip/thigh circumferences were measured. RESULTS: After 30 days, subjects receiving Phaseolus vulgaris extract with a carbohydrate-rich, 2000- to 2200-calorie diet had significantly (p<0.001) greater reduction of body weight, BMI, fat mass, adipose tissue thickness, and waist,/hip/ thigh circumferences while maintaining lean body mass compared to subjects receiving placebo. CONCLUSION: The results indicate that Phaseolus vulgaris extract produces significant decrements in body weight and suggest decrements in fat mass in the face of maintained lean body mass. PMID: 17299581 [PubMed - indexed for MEDLINE]PMCID: PMC1796956Free PMC Article Free text> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796956/pdf/ijmsv04p0045.pdf Food Chem Toxicol. 2007 Jan;45(1):32-40. Epub 2006 Jul 8. Subchronic oral toxicity of a standardized white kidney bean (Phaseolus vulgaris) extract in rats. Chokshi D. Pharmachem Laboratories, Inc., 265 Harrison Avenue, Kearny, NJ 07032, United States. Abstract Dietary supplements containing "starch blockers" are believed to reduce carbohydrate-derived calories by interfering with alpha-amylase, the digestive enzyme responsible for conversion of complex carbohydrates to simple, absorbable sugars. The present paper reports the findings of a 28-day oral toxicity study in rats of Phase 2, a standardized extract derived from the common white kidney bean (Phaseolus vulgaris), which has been shown to have alpha-amylase-inhibiting activity. In order to establish safety, eighty male and female Sprague-Dawley rats (10 animals/sex/group) received Phase 2 via oral gavage at doses of 0, 625, 1250, and 2500 mg/kg (7 days/wk) for a period of 31 (males) or 32 (females) days. There were no mortalities, clinical signs, body weight or nutritional effects, gross alterations, clinical or histopathological alterations that were considered attributable to test substance administration. Under conditions of this study and based on toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) of Phase 2 was judged to be 2500 mg/kg/day in each sex for administration by oral gavage of a standardized white kidney bean extract, Phase 2 for 28 days. PMID: 17045383 Br J Nutr. 2006 Sep;96(3):539-44. White bean amylase inhibitor administered orally reduces glycaemia in type 2 diabetic rats. Tormo MA, Gil-Exojo I, Romero de Tejada A, Campillo JE. Dpto. de Fisiologia, Facultad de Medicina, Universidad de Extremadura, Apartado de Correos 108, 06071 Badajoz, Spain. Abstract A purified pancreatic alpha-amylase inhibitor (alpha-AI) from white beans (Phaseolus vulgaris) was administered orally (100 mg/kg body weight dissolved in 9 g NaCl/l) for 22 d to non-diabetic (ND) and type 2 diabetic (neonatal diabetes models n0-STZ and n5-STZ) male Wistar rats. Mean glycaemia (mmol/l) declined from day 4 of the alpha-AI administration in ND rats (5.48 (sem 0.08) v. 4.39 (sem 0.13); P<0.05), n0-STZ diabetic rats (7.94 (sem 0.42) v. 5.56 (sem 0.32); P<0.01) and n5-STZ diabetic rats (17.34 (sem 2.58) v. 11.93 (sem 1.96)), until the end of treatment: ND (5.22 (sem 0.21) v. 3.97 (sem 0.06); P<0.01); n0-STZ (8.10 (sem 0.19) v. 5.21 (sem 0.30); P<0.01); and n5-STZ (16.36 (sem 2.14) v. 7.69 (sem 1.34); P<0.01). There was a decrease in water intake (ml/d) in the alpha-AI-treated diabetic rats: n0-STZ (30 (sem 0.10) v. 22 (sem 1.50); P<0.01) and n5-STZ (76 (sem 5.04) v. 57 (sem 4.85); P<0.01). Food intake (g/d) decreased in all three groups: ND (23 (sem 0.31) v. 20 (sem 0.03); P<0.05); n0-STZ (22 (sem 0.55) v. 16 (sem 0.98); P<0.01); and n5-STZ (31 (sem 0.58) v. 23 (sem 1.20); P<0.01). The enterocyte sucrase and maltase activities (U/g proteins) were high (P<0.01) in the untreated diabetic rats, n0-STZ (45 (sem 4) and 152 (sem 10), respectively) and n5-STZ (67 (sem 12) and 151 (sem 10), respectively) with respect to the ND rats (24 (sem 2) and 74 (sem 10), respectively). After alpha-AI treatment, enzyme activities declined in both diabetic rats, n0-STZ (21 (sem 2) and 85 (sem 11); P<0.01) and n5-STZ (28 (sem 7) and 75 (sem 19); P<0.05), to values close to those in the ND rats. In conclusion, alpha-AI significantly reduced glycaemia in both the ND and diabetic animals and reduced the intake of food and water, and normalized the elevated disaccharidase levels of the diabetic rats. PMID: 16925860 Br J Nutr. 2004 Nov;92(5):785-90. Hypoglycaemic and anorexigenic activities of an alpha-amylase inhibitor from white kidney beans (Phaseolus vulgaris) in Wistar rats. Tormo MA, Gil-Exojo I, Romero de Tejada A, Campillo JE. Department of Physiology, Faculty of Medicine, University of Extremadura, 06701 Badajoz, Spain. Abstract An inhibitor of alpha-amylase was isolated and purified from an extract of white kidney beans (Phaseolus vulgaris). The acute oral administration of the inhibitor (50 mg/kg body weight) to adult Wistar rats together with a starch load (2 g/kg body weight suspended in NaCl (9 g/l)) reduced the increase in glycaemia over the basal value (NaCl, 222 (SEM 49); inhibitor, 145 (SEM 16) mmol/l x 180 min; P<0.05) without modifying the insulin response. On administering the inhibitor orally (50 mg/kg body weight dissolved in NaCl (9 g/l)) for 21 d to rats fed on a standard diet, a decline was observed in the glycaemia values on day 0 (NaCl, 5.53 (SEM 0.12); inhibitor, 5.25 (SEM 0.16) mmol/l) relative to those obtained on days 10 (NaCl, 5.00 (SEM 0.14); inhibitor, 4.60 (SEM 0.08) mmol/l; P<0.05) and 21 (NaCl, 5.22 (SEM 0.22); inhibitor, 4.50 (SEM 0.12) mmol/l; P<0.01) of treatment, without modifying the plasma concentration of insulin. There was found to be a significant anorexigenic action of the inhibitor; there was reduced food intake (NaCl, 23.07 (SEM 0.31); inhibitor, 19.50 (SEM 0.49) g/d; P<0.01), a reduced weight gain (NaCl, 52 (SEM 3); inhibitor, -1.33 (SEM 8.9) g/21 d; P<0.01), as well as changes in the activity of some intestinal enzymes such as maltase (NaCl, 87 (SEM 7); inhibitor, 127 (SEM 11) U/g proteins; P<0.05). The present study has shown, for the first time, that the prolonged administration of an alpha-amylase inhibitor reduces blood glucose levels and body-weight gain in Wistar rats. PMID: 15533267 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32567