Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since impaired glucose tolerance (IGT) is a major risk factor for non-insulin-dependent diabetes mellitus (NIDDM), some kinds of intervention aiming to prevent or to delay the onset of NIDDM in subjects with IGT might be considered. Besides life style modification, drug therapy which could correct insulin deficiency and insulin resistance, might prevent progression to NIDDM. One agent is an alpha-glucosidase inhibitor, which delays the absorption of glucose from the intestine. The resulting decrease in postprandial hyperglycemia and hyperinsulinemia could theoretically decrease insulin resistance in IGT subjects and, it is hoped, prevent or delay progression to NIDDM. Metformin, an antihyperglycemic drug of the biguanide class, may be effective in subjects with IGT by reducing hepatic glucose output, enhancing insulin sensitivity, or through other mechanisms such as weight loss. New insulin sensitizers, such as troglitazone and pioglitazone, improve insulin-mediated glucose disposal by enhancing tissue sensitivity to the actions of insulin and reversing the insulin resistance, characteristic of NIDDM. Sulfonylureas might be another candidates of drug intervention to IGT whose insulin secretory abilities are markedly reduced. As far as the question, "Can NIDDM be prevented or delayed?" is concerned, a prospective study using life style modification or above-mentioned drugs, should be performed on long-term basis.
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PMID:[Drug therapy in subjects with impaired glucose tolerance]. 891 39

Over the past few years, several oral agents for the treatment of type 2 diabetes have become available in the United States. Metformin, a biguanide that has been used for decades in other countries throughout the world, improves glycemic control without exacerbating hyperinsulinemia or promoting weight gain. This agent has recently been reintroduced in the United States. Acarbose is an alpha-glucosidase inhibitor that improves glycemic control by decreasing the intestinal absorption of glucose, thereby decreasing postprandial glucose elevations. The use of metformin and acarbose may be limited by their side effects and potential risks, especially the risk of lactic acidosis with metformin. The third newly available agent, troglitazone, has been shown to improve insulin sensitivity. Combinations of metformin, acarbose and troglitazone may facilitate improved glycemic control without the use of insulin, or they may allow sulfonylurea or insulin dosages to be reduced, in this way minimizing the adverse effects of hyperinsulinemia. Unfortunately, current oral therapies do not prevent the inevitable decline in glycemic control that occurs during the natural history of type 2 diabetes.
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PMID:New oral therapies for type 2 diabetes. 937 Oct 13

Acarbose is the first of a new class of antidiabetic agents, the alpha-glucosidase inhibitors. Acarbose has proven effectiveness as a first-line drug in type 2 diabetes insufficiently controlled by diet alone. In addition to providing short-term glycemic control, acarbose also reduces HbA1c levels. This effect is greatest when therapy is initiated early in the disease and when baseline HbA1c levels are high. Depending on the baseline HbA1c value, therapeutic doses of acarbose lead to a HbA1c reduction of 0.5%-1.2%. Acarbose may be safely combined with all oral hypoglycemic agents, and has been found to have utility as an adjunct to sulfonylurea and metformin therapy. It also improves control of insulin-treated type 2 diabetes and enables a reduction of exogenous insulin requirements of up to 30%. Acarbose also has beneficial effects on the coronary risk factors, e.g. postprandial triglyceride levels, elevated cholesterol, and hyperinsulinemia. The early phase of acarbose therapy may be associated with side effects such as meteorism, flatulence, and diarrhea. These result from the local effect of the drug and decline with time. To date, there have been no reports of systemic toxicity. Acarbose does not cause hypoglycemias or weight gain.
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PMID:The role of acarbose in the treatment of non-insulin-dependent diabetes mellitus. 964 42

The JCR:LA-cp rat is one of a number of strains incorporating the autosomal recessive cp gene that induces obesity. This strain is unique in the development of not only a profound insulin resistance, but an accompanying cardiovascular disease that correlates strongly with hyperinsulinemia. The hyperinsulinemia develops rapidly after 4 weeks of age, with an age at half-maximum of 5.5 weeks. This reflects postprandial plasma insulin levels that peak at 1000 mU/l in a standardized meal tolerance test. Defective acetylcholine-mediated vascular relaxation develops with a 1-week lag over the developing hyperinsulinemia. The frequency of staining for the vascular adhesion molecules, VCAM-1 and ICAM, does not show either age or genotype variation, although plasma levels do show an age variation. Treatment of the rats with the alpha-glucosidase inhibitor, miglitol (Bay m1099), obviates the exaggerated postprandial glucose and, especially, the insulin responses of the cp/cp rat. This causes an improvement in insulin sensitivity, prevention of the impaired vascular relaxation, and reduction in plasma levels of advanced glycated end-products. Arterial wall morphology, as visualized by both scanning and transmission electron microscopy, shows abnormal endothelium, adherent macrophages, and activated migrating smooth muscle cells in the intima. Oil-Red-O staining reveals lipid deposits in the intimal spaces, as confirmed by the presence of foam cells. The lesions resemble fatty streaks or modest atherosclerosis in man, rather than the extensive cholesterol-laden lesions seen in familial hypercholesterolemia or cholesterol-fed rabbit models. The lean rats of the strain show similar, but less marked, intimal abnormalities. The vasculopathy in this animal model appears to be precipitated by the developing hyperinsulinemia, but also requires an underlying abnormality of vascular smooth muscle and possibly also of the endothelium.
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PMID:Vasculopathy and insulin resistance in the JCR:LA-cp rat. 967 79

The JCR:LA-cp rat is one of a number of strains that carry the mutant autosomal recessive cp gene. Animals, of all strains, that are homozygous, for the gene (cp/cp) become obese, insulin resistant, and hypertriglyceridemic. Heterozygotes or homozygous normal rats (+/+) are lean and metabolically normal. The JCR:LA-cp rat is unique in the development of a frank vasculopathy with atherosclerotic lesions and associated ischemic myocardial lesions. The cardiovascular disease is strongly correlated with the hyperinsulinemia, which develops as the animals mature from 4 to 8 weeks of age. The hyperinsulinemia can be decreased by marked food restriction, ethanol consumption, or reduction of the postprandial glucose and insulin responses through the use of alpha-glucosidase inhibitors. Any treatment that reduces plasma insulin levels is associated with a reduction in cardiovascular disease. In contrast, a reduction in plasma triglyceride concentrations, alone, has no effect on end-stage lesions. JCR:LA-cp rats, particularly those that are cp/cp, are, however, sensitive to cholesterol in the diet, unlike other strains that are highly resistant. Further, the rats have abnormal vascular smooth muscle cells that, especially in the cp/cp animals, are hyperplastic and activated and migrate into the intimal space. Our findings suggest that susceptibility to cardiovascular disease requires hypermsulinemic stress coupled with excessive dietary intake and the presence of one or more other necessary, but not sufficient, genetic factors. One of these may be a genetic abnormality of vascular smooth muscle cells. A similar situation may occur in humans.
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PMID:Cardiovascular disease in the JCR:LA-cp rat. 982 17

The C57BL/6 (B6) mouse is more sensitive to the effects of a high-fat diet than the A/J strain. The B6 mouse develops severe obesity, hyperglycemia, and hyperinsulinemia when fed this dietary regimen. This study was conducted to determine the effects of dietary fat and sucrose concentrations on body composition and intestinal sucrase (EC 3.2.1.48) and maltase (EC 3.2.1.20) activity in these two mouse strains. High-fat diets, regardless of sucrose content, resulted in significant weight gain, higher body fat, and lower body protein and water content in both strains of mice. The shift toward higher body fat and lower protein and water content was far greater in the B6 strain. Low-fat, high-sucrose diets resulted in lower body weight in both strains, as well as significantly greater body protein content in B6 mice. Analysis of intestinal sucrase showed that the enzyme was less active in B6 mice when the diet was high in sucrose. Both sucrase and maltase had lower activity in the presence of high dietary fat in both mouse strains. The percent reduction of intestinal enzyme activity due to dietary fat was similar in both strains. The B6 mouse exhibits disproportionate weight gain and altered body composition on a high-fat diet. This coupled with the reduced body weight and increased body protein on a low-fat, high-sucrose diet suggests that factors-relative to fat metabolism rather than sucrose metabolism are responsible for obesity.
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PMID:Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. 982 12

The recently developed Otsuka Long-Evans Tokushima Fatty (OLETF) rat is known to develop insulinopenic diabetes after a prolonged period in a condition resembling non-insulin-dependent diabetes mellitus (NIDDM). We examined the effect of pharmacological intervention with a potent intestinal alpha-glucosidase inhibitor, acarbose, on the metabolic and histopathologic changes in this rat model. The first two groups of rats received an acarbose-rich diet (150 mg/100 g normal chow) from 12 weeks of age (ie, before the onset of diabetes) or from 28 weeks of age (ie, after the onset of diabetes), while a third group received the acarbose-rich diet for the initial 16 weeks only (from 12 to 28 weeks of age). A control group received standard rat chow. Acarbose-fed rats gained less weight or lost weight despite increased food intake when switched to the acarbose-rich diet. Acarbose also reduced visceral adipose depots and fasting triglyceride (TG), glucose, and insulin levels. At the end of the study at 72 weeks, the pancreatic wet weight and insulin content were significantly higher in the treated groups versus control rats. The morphological changes observed in control rats, such as atrophy of the pancreas and reduced number and size of islets, were not present in acarbose-treated rats. Rats fed acarbose from 12 to 28 weeks of age gradually gained weight after switching to standard chow, and hyperinsulinemia, hyperglycemia, and hyperlipidemia appeared (in that order). The pancreatic insulin content in these rats was significantly higher and the visceral adipose depot was significantly smaller than in control rats. Our study demonstrates that acarbose prevented and reversed the metabolic derangement and histopathological changes in genetically diabetic rats. Moreover, treatment with acarbose even for a short period produced a marked delay in the development of insulin insensitivity and frank diabetes.
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PMID:Metabolic abnormalities in the genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty rat can be prevented and reversed by alpha-glucosidase inhibitor. 1009 12

Gastrectomy or vagotomy may result in reactive hypoglycemia, which, in some cases, can reduce the plasma glucose levels to 30-40 mg/dl due to rapid digestion and absorption of food, especially carbohydrates. It also occurs sometimes in patients on hemodialysis, where it is a potentially lethal complication. Because insulin has a longer half-life due to lack of renal degradation, hypoglycemia can be induced by insulin in patients with renal failure. We treated a patient with frequent episodes of severe hypoglycemia, that were sometimes accompanied by convulsions. He had undergone total gastrectomy 8 years before and had been maintained on hemodialysis for 3 years. Hyperinsulinemia caused by oxyhyperglycemia associated with post-gastrectomy led to severe hypoglycemia in this patient because of the lack of renal insulin degradation. Since nutritional treatment did not successfully manage his reactive hypoglycemia, an alpha-glucosidase inhibitor, acarbose, was administered to treat his oxyhyperglycemia. This therapy was very effective and he has not had any recurrence of reactive hypoglycemia since the initiation of the therapy.
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PMID:Treatment with alpha-glucosidase inhibitor for severe reactive hypoglycemia: a case report. 1107 24

In this review we present the agents that are in use in the treatment of type 2 diabetes. Sulfonylureas of the 1st and 2nd generation increase insulin secretion but can induce hyperinsulinemia and sometimes prolonged hypoglycemia. Glimepiride is a new 3rd generation sulfonylurea with some advantages over the other members of this group, such as a lower risk of hypoglycemia, no interaction with cardiovascular KATP-channels and a possibility that it may increase insulin sensitivity. There are also newer insulin secretagogues (such as neteglinide and repaglinide) with a rapid onset of action on the beta-cell, therefore inducing a more physiological profile of insulin secretion during meals. The category of insulin sensitizers includes metformin and thiazolidinediones. Metformin effectively reduces hyperglycemia, hyperlipidemia and macroangiopathy in patients with type 2 diabetes. This agent increases the sensitivity of the liver and peripheral tissues to insulin and, therefore, it could be considered as a drug of choice for the prevention of type 2 diabetes. Thiazolidinediones (rosiglitazone and pioglitazone) increase the sensitivity of the tissues to insulin. This mechanism of action makes them powerful therapeutic tools for the treatment of type 2 diabetes (and possibly other insulin resistant states) either alone or in combination with other oral agents. The category of agents that interfere with the absorption of glucose and lipids includes alpha-glucosidase inhibitors (acarbose and miglitol) and lipase inhibitors (or-listat). alpha-Glucocidase inhibitors improve the time relationship between plasma insulin and glucose increases after a meal. Therefore, these agents may be used in the treatment of patients with type 2 diabetes, either alone at a very early stage of this disease (when insulin secretion is still adequate), or in combination with insulin secretagogues. alpha-Glucosidase inhibition may also prove useful as a supplement to insulin therapy in patients with type 1 diabetes mellitus. The inhibitor of gastrointestinal lipase orlistat may prove a useful adjunct to hypocaloric diets in patients with type 2 diabetes and obesity.
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PMID:Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers. 1146 May 77

A water-soluble Touchi-extract (TE) exerts a potent inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs, and elicited anti-glycemic effects in rats and humans with single-bolus oral administration. In the present study, genetically modified diabetic model KKAy mice were used to examine the long-term effects of TE. Eight-week-old male KKAy mice were fed with CE-2 chow containing 0.08 and 0.4% of TE for 60 days. In the latter group, fasting blood glucose levels decreased (6.68 +/- 0.41 mmol/L) significantly (p<0.05) after a 60-day ingestion period compared with controls (8.75 +/- 0.54 mmol/L). Moreover, postprandial blood glucose levels were also significantly reduced (16.79 +/- 2.28 mmol/L; p<0.01) after ingesting TE for only 30 days compared with controls (28.49 +/- 0.59 mmol/L). On oral TE treatment for 60 days, postprandial increases in the blood glucose level after oral loading of sucrose (2 g/kg) at 30 (p<0.05) and 60 (p<0.01) min were significantly depressed compared with controls. Indexes for serum lipids; viz., total cholesterol (p<0.05) and triglyceride (p<0.01) levels significantly decreased after TE ingestion. Indexes for hepatic functions, such as glutamic-oxaloacetic transaminase (p<0.01), glutamic-pyruvic transaminase and gama-glutamyl transpeptide levels, were similarly suppressed. Organ weights of the heart, kidney, jejunum, liver and spleen increased in control KKAy mice due to hyperinsulinemia. Interestingly, the respective organ weights decreased (p<0.05, 0.01) and the jejunum length was reduced (p<0.05) significantly in the TE-treated groups. All in all, TE demonstrated an anti-hyperglycemic effect and may have potential use in the management of non-insulin-dependent diabetic mellitus.
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PMID:Fermented soybean-derived Touchi-extract with anti-diabetic effect via alpha-glucosidase inhibitory action in a long-term administration study with KKAy mice. 1178 46


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