Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was taken 32 male Wistar rats, weighting between 130 g and 150 g, free feeding, to study the total and specific activities of lactase, invertase and maltase of small intestine of rats. The animals were divided by chance in 3 experimental and 1 control group. 1. group--Aloxanic diabetes rats: treated with 1 unit of NPH insulin every day: after the 4th day of aloxane administration, all rats were killed. 2. group--Aloxanic diabetes rats--treated for 5 days with 1 unit of NPH insulin every day; after the 5th day until the 7th they were treated with 4 units of NPH insulin and were also killed. 3. group--Hyperinsulinism rats--Normal rats were treated for 4 days with 4 units of NPH insulin every day. After the 5th day they were killed. 4. group--Control group--Normal rats, free feeding. They were observed during 4 days and were also killed. The results showed that none difference was observed in the 4 groups of rats about the total and specific activities of lactase, invertase and maltase of the small intestine. In this study, all the animals with aloxanic diabetes were treated with insulin. Then, it is possible that the insulin inhibited the stimulator effect of the diabetes upon the dissacaridases of the small intestine of the rats.
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PMID:[Insulin and disaccharidases levels of the small intestine of the rat (author's transl)]. 74 51

AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKA(y), were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22 mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21 mg/kg. Four-week-old female KKA(y) mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKA(y) mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). 162 84

We examined GLUT-4 glucose transporter protein and mRNA in muscle tissue from a new rodent model of non-insulin-dependent diabetes mellitus (NIDDM), the male obese Zucker diabetic fatty (ZDF) rat [ZDF/Drt-fa(F10)]. We also determined whether prevention of hyperglycemia might affect GLUT-4 expression by feeding the intestinal alpha-glucosidase inhibitor acarbose (40 mg/100 g diet) in the diet of male ZDF rats for 19 wk, starting at least 1 wk before the onset of diabetes. Fasting glucose was four- to sixfold greater in diabetic ZDF rats (24.1 +/- 6.7 mM) compared with lean or obese nondiabetic rats. Fasting insulin in diabetic ZDF rats (0.5 +/- 0.1 ng/ml) was similar to lean rats (0.4 +/- 0.1) but greatly reduced compared with obese nondiabetic rats (18.7 +/- 4.0 ng/ml). Acarbose treatment significantly reduced fasting glucose levels to 13.4 +/- 1.4 mM, while insulin levels increased to 1.6 +/- 0.3 ng/ml. GLUT-4 protein levels in diabetic ZDF rats were reduced approximately 40% in red quadriceps and mixed gastrocnemius muscles but were unchanged in white quadriceps muscle. Acarbose treatment was associated with a twofold increase in GLUT-4 protein and mRNA in mixed gastrocnemius muscle. These data indicate that, in this obese model of NIDDM without hyperinsulinemia, there is reduced muscle GLUT-4 protein in red but not white muscle fiber types. The decrease in muscle GLUT-4 expression in this model of NIDDM can be prevented by acarbose treatment, which reduces hyperglycemia and increases beta-cell responsiveness.
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PMID:Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa). 176 39

Retardation of meal carbohydrate absorption by inhibition of starch degradation improves glucose tolerance in normal and diabetic humans. To determine the effects of Bay-m-1099, a new alpha-glucosidase inhibitor, on insulin requirements and prandial glucose tolerance in patients with insulin-dependent diabetes mellitus (IDDM), plasma glucose, triglyceride, and free insulin concentrations were measured after ingestion of a standard breakfast, lunch, and dinner in nine patients with IDDM in a single-blind, randomized, crossover design. A 20% reduction in insulin was given 30 minutes before the meals when the subjects received Bay-m-1099 (50 mg). This resulted in the AUC for plasma insulin to be significantly less with Bay-m-1099 (AUC, 8.2 +/- 1.3 vs. 12.8 +/- 1.6 microU/ml/min with placebo; P less than 0.01). Despite this reduction in plasma insulin levels, postprandial plasma glucose concentrations were reduced for the breakfast (73 +/- 15 vs. 112 +/- 14 mg/dl/min with placebo; P less than 0.01) and dinner (23 +/- 8 vs. 4 +/- 1 mg/dl/min with placebo; P less than 0.05) meal with Bay-m-1099. Bay-m-1099 did not affect postprandial plasma triglycerides and was well tolerated, the major side effect being flatulence (4/9) and mild diarrhea (4/9). We conclude that inhibition of intestinal alpha-glucosidases by Bay-m-1099 in IDDM reduces meal insulin requirements by at least 20% and that such an agent could be useful in the management of diabetes mellitus by reducing hyperinsulinemia.
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PMID:A new alpha-glucosidase inhibitor (Bay-m-1099) reduces insulin requirements with meals in insulin-dependent diabetes mellitus. 331 50

In patients with diabetes mellitus, delayed increases in circulating insulin levels followed by prolonged hyperinsulinemia due to slow absorption of subcutaneously administered insulin hinders maintenance of euglycemia. To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an alpha-glucosidase inhibitor (Acarbose Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion. When 25% less insulin (9 v 12 units) was given along with Acarbose 30 minutes prior to meal ingestion, postprandial hyperglycemia decreased by 45% (areas under the curve, AUC, 8193 +/- 1960 v 14783 +/- 2260 mg/dL X min, P less than 0.02). When similar amounts of insulin (12 units) were given immediately prior to meal ingestion, postprandial hyperglycemia decreased 55% (AUC 6187 +/- 2240 v 13642 +/- 1579 mg/dL X min, P less than 0.001). These results indicate that delay in carbohydrate absorption improves the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and may permit satisfactory postprandial glycemic control when insulin is administered immediately prior to meal ingestion. Thus, an agent like Acarbose, which delays carbohydrate absorption, may be useful as an adjunct to insulin in the treatment of diabetes mellitus.
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PMID:alpha-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus. 388 97

Inhibition of carbohydrate digestion by the alpha-glucosidase inhibitor acarbose (BAY g 5421)reduces carbohydrate-induced postprandial blood glucose increase and insulin secretion. As a consequence, in feeding experiments sucrose-induced hyperinsulinemia and hypertriglyceridemia in genetically obese (fa,fa) "Zucker" rats were dose-dependently reduced by addition of acarbose to the diet (15-80 mg/100 g feed). The body weight gain was dose-dependently reduced. In short-term experiments with a fat-free diet acarbose not only prevented serum triglyceride and free fatty acid increase in spite of lowered insulin concentrations but also decreased their concentrations below the values obtained on standard feed. Under these conditions there were no significant effects on body weight. Hypertriglyceridemia induced by i.v. injection of the lipoprotein lipase inhibitor Triton WR 1339 was reduced without affecting body weight in "Zucker" rats after 3 days on a fat-free diet supplemented with acarbose. The triglyceride increase was even lower than in animals kept on standard feed. The data demonstrate that acarbose reduces sucrose-induced hypertriglyceridemia in (fa,fa) "Zucker" rats by diminishing VLDL production and/or secretion rather than by increasing VLDL removal from the blood.
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PMID:Reduction of carbohydrate-induced hypertriglyceridemia in (fa,fa) "Zucker" rats by the alpha-glucosidase inhibitor acarbose (BAY g 5421). 704 75

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine. Post-prandial hyperglycemia is common among diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestion, indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with placebo, suggesting that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompanied by the rapid disappearance of sucrose from the upper small intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indicated that AO-128 retards the absorption of carbohydrate and reduces post-prandial hyperglycemia.
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PMID:An alpha-glucosidase inhibitor, AO-128, retards carbohydrate absorption in rats and humans. 758 23

The onset and progression of long-term complications in diabetes mellitus appear to be related to the degree of hyperglycemia and the overall metabolic control. Therefore, an important goal in the therapy of subjects with diabetes is to avoid wide fluctuations in blood glucose concentrations and increases in lipid levels. The first therapeutic maneuver to achieve glycemic control is to establish a correct diet containing complex carbohydrates and an adequate amount of dietary fibers. Dietary fibers are capable of reducing the intestinal uptake of carbohydrates. An additional strategy to reduce the uptake of carbohydrates across the intestine has recently been proposed by Puls et al. This strategy involves the use of inhibitors of alpha-glucosidase, an intestinal enzyme that participates in the breakdown of polysaccharides into disaccharides and monosaccharides. The inhibition of alpha-glucosidase by these agents is competitive and reversible and results in delayed and reduced uptake of carbohydrates across the intestine. This effect attenuates the post-prandial hyperglycemia and subsequent insulin secretory response particularly in subjects with hyperinsulinemia. The compound acarbose is a member of first generation alpha-glucosidase inhibitors. The administration of high doses of acarbose can be associated with side effects such as flatulence, meteorism, abdominal pain, and diarrhea due to the fermentation of non-absorbed carbohydrates in the intestinal lumen. Usually, these effects subside following a few days of therapy and/or reduction of the initial dose. Acarbose has been effectively used to treat type 2 diabetic patients either as a first choice drug or in association with sulfonylurea agents and in type 1 diabetics in association with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[alpha-Glucosidase inhibitors in the therapy of diabetes mellitus]. 856 69

This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.
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PMID:Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects. 863 48

Antiobesity and antidiabetic actions of the alpha-glucosidase inhibitor AO-128 were examined using genetically obese-diabetic rats, Wistar fatty. Ten-week-old, male fatty rats were kept on CE-2 diet containing 10 or 25 ppm of AO-128 for 4 weeks. The average drug intake was calculated to be 0.74 or 1.78 mg/kg/day from the average food intake, respectively. The intestinal maltase and sucrase activities were decreased by AO-128 in a dose-related fashion. Food intake of fatty rats treated with AO-128 was decreased throughout the experiment. This decrease in food intake could hardly be explained only by diarrhea which occurred for the first 5 days of the administration of AO-128. AO-128 normalized hyperglycemia and markedly reduced hypertriglyceridemia and hyperinsulinemia in fatty rats. In addition, AO-128 decreased body weight gain, food efficiency, epididymal adipose tissue weight, carcass weight, and body fat deposition. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:AO-128, alpha-glucosidase inhibitor: antiobesity and antidiabetic actions in genetically obese-diabetic rats, Wistar fatty. 869 66


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