X-Message-Number: 32567
Date: Fri, 23 Apr 2010 19:07:16 -0700 (PDT)
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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

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