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)

This report presents a complex analysis of changes proceeding in the gut, blood and internal organs of rats with induced oxidative stress, glucose intolerance and hyperlipidemia after dietary supplementation with an extract from black chokeberry (Aronia melanocarpa) fruit, that is a condensed source of polyphenols (714 mg/g), especially anthocyanin glycosides (56.6%). The disturbances mimicking those observed in metabolic syndrome were induced by a high-fructose diet and simultaneous single injection of streptozotocin (20 mg/kg). Dietary supplementation with the chokeberry fruit extract (0.2%) decreased activity of maltase and sucrase as well as increased activity of lactase in the mucosa of the small intestine. Its ingestion led also to the improvement of antioxidant status, especially, the concentration of a lipid peroxidation indicator (TBARS) in organ tissues (liver, kidney and lung) was normalized; some cholesterol-lowering and distinct hypoglycemic actions were also observed. The mechanism of glucose reduction is likely to be multifactorial, and we suggest the factors related with the decreased activity of mucosal disaccharidases important for further investigation. In conclusion, chokeberry fruit derivatives may act as a promising supplementary therapeutic option in the prevention and treatment of disorders occurring in metabolic syndrome, as well as their complications.
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PMID:Ingestion of black chokeberry fruit extract leads to intestinal and systemic changes in a rat model of prediabetes and hyperlipidemia. 1872 60

In this study, streptozotocin-induced severely diabetic rats and streptozotocin-nicotinamide-induced mildly diabetic rats were established to compare their characteristics and to investigate the hypoglycaemic effects of antidiabetic drugs. Results show that in streptozotocin-induced severely diabetic rats, the pancreatic insulin content decreased to approximately 10% of that in normal rats. These severely diabetic rats also exhibited marked hyperglycaemia and impaired glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in streptozotocin-nicotinamide-induced mildly diabetic rats. These mildly diabetic rats exhibited moderate hyperglycaemia and impaired glucose tolerance due to loss of early-phase insulin secretion. Voglibose (alpha-glucosidase inhibitor), metformin (biguanide), glibenclamide (sulfonylurea), sitagliptin (dipeptidyl peptidase-4 inhibitor) and insulin significantly improved glucose tolerance in streptozotocin-nicotinamide-induced mildly diabetic rats. In contrast, in streptozotocin-induced severely diabetic rats, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results suggest that streptozotocin-nicotinamide-induced mildly diabetic rats, which exhibit a mild decline in glucose tolerance due to loss of early-phase insulin secretion, are sensitive to the hypoglycaemic effects of insulinotropic agents and have many pathological features resembling type 2 diabetes, which may be useful in the pharmacological investigation of numerous antidiabetic drugs.
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PMID:Hypoglycaemic effects of antidiabetic drugs in streptozotocin-nicotinamide-induced mildly diabetic and streptozotocin-induced severely diabetic rats. 1879 71

The STOP-NIDDM trial was an international, double-blind, placebo-controlled randomised study in people with impaired glucose tolerance (IGT). They were treated with an alpha-glucosidase inhibitor, acarbose, to prevent diabetes; the overall number needed to treat (NNT) was 11. In a secondary analysis, we considered the impact of single traits and overall metabolic syndrome (MetS) respectively on risk of diabetes and NNT respectively. In all, there were 1,368 patients. They were followed up for 3.3 years, and the prevalence of MetS was 61%. Multivariate analysis revealed treatment group 2-hour (post-challenge) plasma glucose, glycosylated haemoglobin (HbA1C), triglycerides and leukocyte count as independent predictors. The annual incidence of diabetes in the placebo group with MetS was 18.7% vs. 11.2% in patients without MetS; the corresponding figures in the acarbose group were 13.5% and 9.4%, respectively. The NNT in patients was 5.8 in patients with MetS and 16.5 in those without MetS. In conclusion, most single traits and overall MetS label a very high-risk group in people with IGT. People with MetS reach a NNT to prevent development of new diabetes with acarbose of 5.8.
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PMID:Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial. 1915 26

Diabetes is associated with an increase risk for cardiovascular disease (CVD). Recently, macrovascular complications of diabetes have been shown to start before the development of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since postprandial hyperglycemia and insulin resistance are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial hyperglycemia as well as insulin resistance is a therapeutic target for the prevention of CVD in these high-risk patients. Acarbose, an alpha-glucosidase inhibitor, delays the absorption of carbohydrate from the small intestine, thereby reducing postprandial hyperglycemia. Further, recently, acarbose has been shown to improve insulin resistance in vivo. These findings suggest that acarbose is a promising metabolic modifier that could reduce the risk of CVD in patients with the metabolic syndrome. In this paper, we review the clinical utility of acarbose in various cardiometabolic disorders.
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PMID:Clinical utility of acarbose, an alpha-glucosidase inhibitor in cardiometabolic disorders. 1927 50

The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.
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PMID:Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system. 1968 50

The detrimental effects of a sedentary lifestyle and poor dietary habits are having a significant negative impact on health statistics, with obesity and its attendant risks becoming a major problem in most developed nations, including Japan. Interventions which prevent or delay the development of type 2 diabetes have the potential to reduce the morbidity and mortality associated with the disease and, as a consequence, related healthcare costs. The study conducted to assess whether alpha-glucosidase inhibitor, voglibose could prevent type 2 diabetes developing in high-risk Japanese subjects with impaired glucose tolerance (IGT). 1,780 eligible subjects received standard diet and exercise therapy, and 897 were randomised to receive voglibose and 883 placebo. The study was planned for treatment to be continued until participants developed type 2 diabetes [primary endpoint; determined by bi-annual oral glucose tolerance tests (OG'Ts) as well as fasting blood glucose measured every 3 months] or normoglycaemia or for a minimum of 3 years, subject to the findings of an interim analysis. The interim analysis significantly favoured voglibose and end-of-study report involves individuals treated for an average of 48.1 weeks. Subjects treated with voglibose had a significantly lower risk for the progression to type 2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also, significantly more subjects in the voglibose group achieved normoglycaemia compared with those in the placebo group (599/897 vs 454/881: hazard ratio 1.539). Voglibose, in addition to standard care with diet and exercise, was effective in preventing the progression of IGT to type 2 diabetes and in increasing the proportion of individuals with normoglycaemia in high-risk Japanese subjects with IGT.
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PMID:[Alpha-glucosidase inhibitor for the prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese subjects with impaired glucose tolerance]. 1976 22

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes, exhibits obesity, hyperglycemia and hyperlipidemia, with late onset of chronic and slowly progressive hyperinsulinemia. In this study, we examined effects of long-term dietary supplementation with the alpha-glucosidase inhibitor miglitol on the development of diabetes and the reduction of beta-cells in the pancreas of OLETF rats. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 65 weeks from pre-onset stage (5 weeks old). The non-fasting blood glucose concentrations gradually increased in OLETF rats fed the control diet and, at week 64, were significantly higher than those in OLETF rats fed the miglitol diet and age-matched Long-Evans Tokushima Otsuka (LETO) rats, which are control, non-diabetic, non-obese rats of the same strain. Oral glucose tolerance tests revealed that OLETF rats fed the control diet showed pronounced impaired glucose tolerance, but those fed the miglitol diet did not. Furthermore, insulin concentrations after glucose-loading were significantly lower in OLETF rats fed the control diet than in those fed the miglitol diet. The islets of 65-week-old OLETF rats fed the control diet showed significant fibrosis and loss of beta-cells, while those of age-matched control LETO rats had a normal appearance. Feeding OLETF rats a miglitol diet reduced fibrosis and the loss of beta-cells. Our results suggest that dietary supplementation with miglitol from pre-onset stage in OLETF rats delays the onset and development of diabetes and preserves the insulin secretory function of pancreatic islets.
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PMID:The alpha-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic beta-cells in OLETF rats. 1981 42

Diabetes is associated with an increased risk of cardiovascular disease. It is widely accepted that macrovascular complications start before the development of diabetes. Accumulating evidence shows that impaired glucose tolerance(IGT), a pre-diabetic condition, increases the risk of cardiovascular disease. Mechanistically, postprandial hyperglycemia produces excessive oxidative stress and induces endothelial dysfunction thereby promoting atherosclerosis. Therefore, it is critically important to intervene early on IGT for the prevention of not only diabetes, but also cardiovascular disease. Recent clinical studies have demonstrated that alpha-glucosidase inhibitors that improve postprandial hyperglycemia, can prevent the development of diabetes from IGT. Additionally, alpha-glucosidase inhibitors have been shown to inhibit the progression of cardiovascular disease. This review will focus on the clinical significance of early intervention for IGT with an emphasis on the prevention of cardiovascular disease.
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PMID:[The clinical significance of early intervention for impaired glucose tolerance]. 2044 71

Heat-moisture (hm)-high-amylose corn starch (HACS), which includes a larger amount of resistant starch than HACS or regular cornstarch (CS), is more indigestible in the small intestine than HACS or CS. An hm-HACS diet was also shown to ameliorate glucose intolerance and lipid abnormalities. This study examined the effects of feeding rats an hm-HACS diet for 14 days on the activities of mucosal alpha-glucosidase along the jejunal-ileal axis and lipogenic enzymes in epididymal adipose tissue. The contents in the lumen of the cecum were increased by feeding rats the HACS and hm-HACS diets, and the cecal weight was increased by the hm-HACS diet. The HACS diet reduced the activity of alpha-glucosidase in the upper jejunal mucosa, induced its activity in the upper ileal mucosa, reduced lipogenic enzyme activity in epididymal adipose tissue, and reduced serum triglyceride levels. These effects were more pronounced with the hm-HACS than with the HACS diet. These results suggest that feeding rats the hm-HACS diet reduced the activities of lipogenic enzymes in adipose tissue and alpha-glucosidase in the jejunal mucosa and induced the activity of alpha-glucosidase in the ileal mucosa compared with the HACS diet.
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PMID:Changes in mucosal alpha-glucosidase activities along the jejunal-ileal axis by an Hm-HACS diet intake are associated with decreased lipogenic enzyme activity in epididymal adipose tissue. 2048 69

alpha-glucosidase inhibitors (alphaGIs) increase active glucagon-like peptide-1 (GLP-1) and reduce the total glucosedependent insulinotropic polypeptide (GIP) levels, but their ability to prevent diabetes remains uncertain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, increase active GLP-1 and GIP levels and improve hyperglycemia in a glucose-dependent fashion. However, the effectiveness of their combination in subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) is uncertain. The present study evaluated the effect of miglitol, sitagliptin, and their combination on glucose, insulin and incretin levels in non-diabetic men. Miglitol and sitagliptin were administered according to four different intake schedules (C: no drug, M: miglitol; S: sitagliptin, M+S: miglitol and sitagliptin). The plasma glucose levels were significantly lower for M, S and M+S than for the control. The areas under the curve (AUCs) of the plasma active GLP-1 level in the M, S, and M+S groups were significantly greater than that in the control group. The AUC of the plasma active GLP-1 level was significantly greater for M+S group than for the M and S groups. The AUC of the plasma total GIP level was significantly smaller for M+S group than for the control and M and S groups. The results of our study suggest that miglitol, sitagliptin, or their combination contributes to the prevention of type 2 diabetes.
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PMID:Effects of miglitol, sitagliptin or their combination on plasma glucose, insulin and incretin levels in non-diabetic men. 2051 6


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