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)

The effect of a new complex oligosaccharide (Bay g 5421) of microbial origin on human intestinal alpha-glucosidehydrolase activity was tested in mucosal homogenate from human small bowel biopsy specimens. The alpha-glucosidehydrolase inhibitor (alpha-GHI) exerted a potent inhibitory effect on glucoamylase, sucrase, and maltase, was minimally effective on isomaltase, and did not affect trehalase and lactase activity. Kinetic analysis revealed a fully competitive type of inhibition with a Ki of 1.3 x 10(-6) M; thus the inhibitor had a 15,000-fold higher affinity to the enzyme sucrase than its natural substrate sucrose. The new compound may prove to be useful in the study of carbohydrate maldigestion and malabsorption and may possibly be of therapeutic benefit in diabetes and obesity.
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PMID:Inhibition of human intestinal alpha-glucosidehydrolases by a new complex oligosaccharide. 44 22

Small intestinal morphologic and biochemical changes were studied following jejuno-ileal bypass for obesity after body weight stabilization had occurred. Four patients underwent biopsy of in-continuity and bypassed jejunal and ileal segments of the small intestine 11 to 22 months after the bypass operation. Microscopically, marked mucosal villus hypertrophy of the in-continuity bowel was observed, especially in the ileum. Bypassed jejunal mucosa underwent atrophy compared with pre-bypass jejunum, whereas bypassed ileum appeared similar microscopically to pre-bypass ileum. The specific activities of mucosal disaccharidase enzymes (maltase, sucrase, lactase and trehalase) in units per mg protein remained similar to pre-bypass levels in segments of the in-continuity jejunum and the bypassed jejunum and ileum. On the other hand, elevated mucosal disaccharidase levels were measured in biopsy specimens of the in-continuity ileum. Total enzyme activity per unit length of intestine, however, was estimated to be elevated in both in-continuity jejunum and ileum secondary to mucosal villus hypertrophy. These data indicate that following small bowel bypass: (1) the in-continuity ileum undergoes greater biochemical and morphologic adaptation than the jejunum; and (2) intraluminal nutrients and chyme appear to be essential to maximal intestinal adaptation.
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PMID:Gastrointestinal adaptation following small bowel bypass for obesity. 87 Dec 20

The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose.
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PMID:Management of non-insulin-dependent diabetes mellitus. 128 May 75

Glycosidases are lysosomal enzymes that participate in the catabolism of glycoproteins and other glycoconjugates, and in some way may modify their activity in situations in which carbohydrate metabolism could be altered, such as the case of obesity. Using a fluorometric assay, a study was made of four glycosidase activities: N-acetyl-beta-D-hexosaminidase (NAG), alpha-mannosidase and alpha- and beta-glucosidase in the serum, pancreas, liver and kidney of 22 Zucker fa/fa genetically obese rats and of 23 fa/? controls, both with ages ranging between 13 and 15 weeks. After 12-14 hours fast and prior anaesthesia with sodium pentobarbital intraperitoneally, blood and the afore-mentioned organs were removed for enzymatic study of the serum and the organs after homogenization and centrifugation. In the serum a statistically significant increase in alpha-mannosidase (p < 0.0001) and alpha-glucosidase (p < 0.02) activities was found in the fa/fa obese rats as compared with the controls. No statistically significant differences were found in serum hexosaminidase activity between the two groups, and no serum beta-glucosidase enzymatic activity was detected. In liver, a decrease was observed in hexosaminidase (p < 0.002) and alpha-glucosidase (p < 0.01) activities in the obese rats as compared with the controls. In whole pancreas an increase was found in alpha-glucosidase activity in the obese rats with respect to the controls (p < 0.001), with no statistically significant differences in the hexosaminidase, alpha-mannosidase and beta-glucosidase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enzymatic glycosidase activities in experimental obesity. 142 11

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

1. Groups of lean and obese LA/N-cp and obese Type II diabetic SHR/N-cp rats were fed semisynthetic diets with or without the alpha-glucosidase inhibitor acarbose (ACB, 100 mg/kg diet, p.o.) from 8 until 15 weeks of age, and measures of fasting serum total cholesterol (TC), insulin (INS), and hepatic HMG-CoA synthase activity determined at the end of the study. 2. ACB was without marked effect on mean food intake in either strain or either phenotype, and resulted in less weight gain and decreased adipose mass in obese LA/N-cp rats. INS was greater in the obese than the lean phenotype of both strains, and ACB resulted in greater reductions in INS in obese LA/N-cp than in obese LA/N-cp rats. 3. Serum TC concentrations were greater in the obese than in the lean phenotype of both strains, and ACB resulted in decreases in TC in both strains and in lower beta:alpha lipoprotein cholesterol ratios in obese LA/N-cp rats. Liver HMG Co-A synthase activity was greater in lean than obese rats and ACB resulted in normalization of enzyme activity in obese LA/N-cp but not SHR/N-cp rats. 4. These results confirm the hypercholesterolemia which occurs in the obese phenotype of the corpulent rat strains, and indicates that ACB may bring about significant reductions in body weight and fatness, TC, and in improved beta:alpha lipoprotein ratios and HMG-CoA synthase activity in obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of the intestinal glucosidase inhibitor acarbose on cholesterogenesis in corpulent rats. 168 84

The activities of intestinal disaccharidases are known to be responsive to changes in the dietary intake of carbohydrates in the adult rat. Little is known, however, regarding the activities of these enzymes in obese subjects and how they are affected by differing carbohydrate intakes. To evaluate the effect of carbohydrate intake on the activity of intestinal disaccharidases in obesity, we used the genetically obese mouse C57BL/6J obob as an experimental model. Representing an example of early-onset obesity and mature-onset diabetes, this animal is characteristically hyperinsulinemic and hyperglycemic. Groups of obese mice and lean littermates were fed for 7 weeks equal amounts of either high-dextrose or low-dextrose isoenergetic diets. Sucrase, maltase, and lactase activities were measured on intestinal homogenates from the proximal and middle portions of the jejunoileum (upper and lower jejunum). Results were expressed as activity per tissue protein as well as total activity. Obese mice were found to have consistently greater total activity of both sucrase and maltase than their lean littermates, mostly as a result of increased intestinal size. Total lactase activity, however, was similar in the upper jejunum in both obese and lean mice, largely related to a decreased specific activity in obese mice. All mice fed the high-dextrose diet had significantly increased total activity of all disaccharidases studied when compared to the low-dextrose-fed animals, except for the lactase activity in the lower jejunum, where no differences were found in either group. Increases in activity related to high carbohydrate intake were a result of increases in specific activity.
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PMID:Effect of a high-dextrose diet on sucrase and lactase activity in jejunum of obese mice (C57BL/6J obob). 309 6

Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis (Ro 22-0654). All drugs were presented as diet admixtures over 3 or 4 consecutive days. Total food and water intakes, the temporal pattern of feeding, and the average meal frequency and meal size were measured using computerized data collection procedures. Inhibitors of carbohydrate absorption failed to suppress food intake in either obese or lean Zucker rats and had no effect on the parameters of feeding. In contrast, inhibitors of lipid metabolism reduced food intake by 56-77% by reducing both meal frequency and meal size. Direct inhibition of lipid metabolism may be a viable mechanism for anti-obesity agents.
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PMID:Effects of inhibitors of carbohydrate absorption or lipid metabolism on meal patterns of Zucker rats. 384 Dec 13

Acarbose is an alpha-glucosidase inhibitor which reversibly and competitively inhibits the digestion of oligo- and disaccharides at the brush border of the small intestine. This study evaluates the preventive and therapeutic properties of acarbose in the treatment of obesity. Dose-response experiments were performed during repeated sucrose loads in man in order to investigate the effects of acarbose on plasma insulin and blood glucose levels. After titration of efficient doses, a long-term tolerance test of acarbose was undertaken in a small pilot study. Finally, the relapse preventing effect of acarbose was tested during double-blind cross-over conditions in 24 weight reduced obese women. In growing Sprague-Dawley rats, the effects of acarbose on body weight, lipid depots and adipose tissue cellularity were tested during pair-feeding and ad libitum conditions. Such effects were also studied in adult ad libitum-fed rats. Blood glucose, plasma insulin, body fat, depot lipids as well as fat cell weight and number were determined with established techniques. During a sucrose load, acarbose reduced insulin in a dose-dependent fashion. Glucose was also reduced, but not dose-dependently and only to a moderate extent. During a 200 g sucrose load, 400 mg of acarbose did not necessarily result in a maximal reduction of the insulin response while the glucose response was maximally inhibited after 100 mg. Acarbose reduced the relapse rate after weight reduction. No serious side effects were observed. Flatulence and meteorism occurred frequently. In growing rats, acarbose retarded the development of body weight and of lipid depots not only during pair-feeding conditions but also in ad libitum-fed animals eating considerably more than their controls. The spontaneous food consumption was increased by acarbose also in adult rats but in these animals neither body weight nor lipid depots were significantly reduced by acarbose. It is concluded that acarbose induces a carbohydrate malabsorption. Insulin levels are reduced not only via a decreased glycemic stimulus but also by interference with other insulin releasing mechanism(s). Acarbose is the first drug ever tested with long-term relapse reducing effects after weight reduction. Animal experiments suggest that acarbose may be of value in the prevention of obesity, particularly since the drug retards lipid accumulation also during ad libitum-feeding.
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PMID:alpha-Glucosidase inhibition in obesity. 391 27

The longitudinal distribution of different brush border enzymes along the human small intestine was studied by crossed immunoelectrophoresis. The results are based on biopsies taken every 50 cm in three intestines obtained at autopsy and on peroral or peroperative biopsies from the ligament of Treitz, proximal jejunum and distal ileum from 11 patients undergoing jejunoileal bypass operation for obesity. Lactase-phlorizin hydrolase (EC 3.2.1.23-62) and sucrase-isomaltase(EC 3.2.1.48-10) had their highest level in jejunum with decreasing activity towards the proximal and distal ends of the intestine, while maltase (EC 3.2.1.20) increased along the intestine and reached its highest activity in the distal ileum. A carboxypeptidase (EC 3.4.12.X) is demonstrated as an enzymatic entity of the human intestine. This enzyme had a rather flat distribution curve while microvillus aminopeptidase (EC 3.4.11.2), dipeptidyl peptidase IV (EC 3.4.14.X) and aspartate aminopeptidase (EC 3.4.11.7) all increased along the length axis and reached maximum values in distal ileum.
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PMID:Immunoelectrophoretic studies on human small intestinal brush border proteins--the longitudinal distribution of peptidases and disaccharidases. 611 68


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