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)

Oral acarbose, a competitive inhibitor of alpha-glucosidase, has been shown to be effective in decreasing the postprandial rise in blood glucose and insulin. A double blind, cross-over, placebo controlled, randomized study in poorly controlled, non-insulin dependent diabetic patients under treatment with sulfonylureas was carried out. The patients continued receiving sulfonylureas throughout the study period and were randomly allocated into two sequences. In sequence A they received 100 mg tablets tid during 12 weeks; placebo tid during 2 weeks (wash-out period) and finally they were crossed over to placebo tid during 12 weeks. In sequence B, they received placebo tid 12 weeks, placebo tid during 2 weeks and finally acarbose 100 mg tid during 12 weeks. Sixteen patients were included in each sequence; three were excluded from sequence A, one because of side effects, one because of severe neuropathy and one because of change of address. One was excluded from sequence B because of failure to take the sulfonylurea. A slight but statistically significant decrease in weight was observed with acarbose as compared with placebo in both sequences. Significant reductions in postprandial glucose were observed in both sequences with acarbose. Significant reductions in fasting blood glucose were also observed in some visits. Although lower mean values of triglycerides and HbA1c were observed with acarbose, they were not statistically significant. Acarbose had side effects almost in all patients, but decreased on continued therapy. Only one patient had to be excluded for this cause. Acarbose is a useful therapeutic resource in poorly controlled non-insulin dependent diabetic patients in combination with sulfonylureas.
 ...
PMID:[Efficacy and tolerance to acarbose in non-insulin-dependent diabetics]. 152 53

The development of alpha-amylase and brush-border alpha-glucosidase inhibitors is reviewed. The mode of action as well as pharmacological and pharmacodynamic properties of selected inhibitors with special regard to the most thoroughly investigated alpha-glucosidase inhibitor acarbose are discussed. Inhibition of intestinal alpha-glucosidases delays the digestion of starch and sucrose, flattens the postprandial blood glucose excursions, and thus mimics the effects of dieting on hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. Therefore, the mechanism of alpha-glucosidase inhibition represents the pharmacological optimization of the dietary principle of delayed carbohydrate absorption. In pre-clinical studies using diabetic animals the oral administration of acarbose improved the metabolic state and reduced the blood glucose area under the curve. As a consequence, the process of non-enzymatic glycation of proteins was retarded as indicated by reduced glycated haemoglobin, glomerular basement membranes or advanced glycation end-products (AGEs) in collagen. These improved biochemical parameters correlated with beneficial effects against the development of diabetic nephropathy and neuropathy. Thus, the treatment of diabetic animals with acarbose does not only improve the metabolic state but has also the potential to delay, or possibly prevent, the development of diabetic complications.
 ...
PMID:Pharmacology of alpha-glucosidase inhibition. 800 24

The development of the alpha-glucosidase inhibitor acarbose provides a new approach in the management of diabetes. By competitive and reversible inhibition of intestinal alpha-glucosidases, acarbose delays carbohydrate digestion, prolongs the overall carbohydrate digestion time, and thus reduces the rate of glucose absorption. After oral administration of acarbose, the postprandial rise in blood glucose is dose-dependently decreased, and glucose-induced insulin secretion is attenuated. Because of diminished postprandial hyperglycemia and hyper-insulinemia by acarbose, the triglyceride uptake into adipose tissue, hepatic lipogenesis, and triglyceride content are reduced. Therefore, acarbose treatment not only flattens postprandial glycemia, due to the primary and secondary pharmacodynamic effects, but also ameliorates the metabolic state in general. In diabetic animals, acarbose reduced urinary glucose loss, the blood glucose area under the curve, and prevented the decrease in skeletal muscle GLUT4 glucose transporters. As a consequence of the reduced mean blood glucose area under the curve, the amount of protein nonenzymatically glycated was diminished, as was the formation of advanced glycation end-products (AGEs). The prevention of basement membrane glycation and thickening in various tissues indicated that acarbose treatment of diabetic animals produced beneficial effects against the development of nephropathy, neuropathy, and retinopathy. Thus, the alpha-glucosidase inhibitor acarbose may have the potential to delay or possibly prevent the development of diabetic complications.
 ...
PMID:The mechanism of alpha-glucosidase inhibition in the management of diabetes. 854 17

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.
 ...
PMID:Pharmacologic treatment options for non-insulin-dependent diabetes mellitus. 900 95

The use of insulin in elderly patients raises special considerations. Most people who develop diabetes mellitus late in life have type 2 diabetes mellitus, in which there is some residual endogenous insulin secretion. This pancreatic insulin secretion, when present, stabilises their metabolic status. However, some elderly people lose virtually all their endogenous insulin secretory capacity over time, or may even have type 1 (autoimmune) diabetes mellitus with no endogenous insulin. Generally, older patients with diabetes mellitus can be managed for years, often decades, with nutritional therapy and oral agents. More options exist now than did previously. In addition to a variety of sulfonylureas, there is metformin, troglitazone, and/or alpha-glucosidase inhibitors, that are viable options to be used before turning to insulin. The goals of insulin therapy in the elderly must be considered. When hyperglycaemia causes symptoms (polyuria, polydypsia and bodyweight loss) blood glucose levels are generally >200 mg/dl, and insulin is needed if maximal doses of oral agents have been used. Insulin is also indicated when hyperglycaemia puts patients at risk of hyperosmolar states, for example, when blood glucose is >300 mg/dl during a normal day. Clinical judgement dictates whether to use insulin to control glycaemia in the attempt to avoid long term complications such as neuropathy, retinopathy or nephropathy. In people with relatively short life expectancy, major comorbities and no sign of diabetic complications, the risk may be small. On the other hand, in patients for whom neuropathy, in particular, is a major risk, controlling glycaemia (with insulin if necessary) does reduce that risk. Most patients with type 2 diabetes mellitus can be managed with relatively simple insulin regimens thanks to their endogenous insulin secretion. A single bedtime dose of neutral protamine Hagedorn (NPH) insulin, with or without continuation of daytime oral agents, may control fasting blood glucose. A pre-mix combination of NPH and Regular insulin such as 70/30 or 50/50 may be used pre-meal. More customised, 'intensive' insulin regimens are needed when the glycaemia is unstable. Hypoglycaemia is clearly the most significant risk of insulin therapy. If mild and easily treated, it is of no real concern. On the other hand, nocturnal hypoglycaemia, and, in particular, hypoglycaemia unawareness, are clear signs that the insulin regimen should be modified. In summary, insulin therapy may be necessary, and can be used effectively, in elderly patients. However, risk:benefit considerations must be taken into account when deciding which patients to treat with insulin and what insulin regimen to use.
 ...
PMID:Feasibility and outcomes of insulin therapy in elderly patients with diabetes mellitus. 1040 37

This article reviewed the relevant literature including published clinical trials and reviews on currently available oral hypoglycemic agents. Results showed that the benefits of glycemic control have been established through multiple clinical trials. Long-term control of blood glucose levels in type 1 and type 2 diabetic patients will decrease the incidence and prolong the time until progression of diabetic retinopathy, nephropathy, and neuropathy. Our increased understanding of the pathophysiology behind type 2 diabetes has led to the development of many new agents that are aimed at treating the underlying insulin resistance and relative insulinopenia. The sulfonylureas as a group have been used for many years and act by stimulating insulin secretion. They are useful alone or as combination therapy with insulin or another oral hypoglycemic agent. The biguanides act by decreasing hepatic glucose production and by increasing peripheral insulin sensitivity. The alpha-glucosidase inhibitors act nonsystemically by blocking the metabolism of digested polysaccharides and therefore lowering the amount of carbohydrate absorbed in a meal. Benzoic acid derivatives act in a manner similar to that of sulfonylureas by enhancing pancreatic insulin production. They offer a shorter duration of action, lowering the risk of hypoglycemia. The thiazolidinediones increase peripheral insulin sensitivity and are effective as both monotherapy and combination therapy. Oral hypoglycemic agents, when properly administered, are very effective in controlling type 2 diabetes and preventing long-term complications.
 ...
PMID:New directions in type 2 diabetes mellitus: an update of current oral antidiabetic therapy. 1064 11

Concurrent with the spread of the western lifestyle, the prevalence of all types of diabetes is on the rise in the world's population. The number of diabetics is increasing by 4-5% per year with an estimated 40-45% of individual's over the age of 65 years having either type II diabetes or impaired glucose tolerance. Since the signs of diabetes are not immediately obvious, diagnosis can be preceded by an extended period of impaired glucose tolerance resulting in the prevalence of beta-cell dysfunction and macrovascular complications. In addition to increased medical vigilance, diabetes is being combatted through aggressive treatment directed at lowering circulating blood glucose and inhibiting postprandial hyperglycemic spikes. Current strategies to treat diabetes include reducing insulin resistance using glitazones, supplementing insulin supplies with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors. In all of these areas, new generations of small molecules are being investigated which exhibit improved efficacy and safety profiles. Promising biological targets are also emerging such as (1) insulin sensitizers including protein tyrosine phosphatase-1B (PTP-1B) and glycogen synthase kinase 3 (GSK3), (2) inhibitors of gluconeogenesis like pyruvate dehydrogenase kinase (PDH) inhibitors, (3) lipolysis inhibitors, (4) fat oxidation including carnitine palmitoyltransferase (CPT) I and II inhibitors, and (5) energy expenditure by means of beta 3-adrenoceptor agonists. Also important are alternative routes of glucose disposal such as Na+-glucose cotransporter (SGLT) inhibitors, combination therapies, and the treatment of diabetic complications (eg. retinopathy, nephropathy, and neuropathy). With may new opportunities for drug discovery, the prospects are excellent for development of innovative therapies to effectively manage diabetes and prevent its long term complications. This review highlights recent (1997-2000) advances in diabetes therapy and research with an emphasis on small molecule drug design (275 references).
 ...
PMID:Current therapies and emerging targets for the treatment of diabetes. 1128 51

Screening for diabetes makes good sense in particular in patients with overweight, hypertension or dyslipidemia. For type 2 diabetes is often not recognized until sequelae have put in an appearance. Consideration must be given to the possible presence of neuropathy, micro- and macroangiopathy and cardiovascular and cerebral disease. The primary therapy recommendations for type 2 diabetics comprise diet, weight loss and increased exercise. Depending on the success of these measures and the patient's constitution, medication with biguanides, sulfonylureas, glinides, glitazones alpha-glucosidase inhibitors or, where indicated, insulin, is then applied.
 ...
PMID:[Newly diagnosed diabetes mellitus--what to look out for]. 1534 29

Numerous glycogenosomes were found in the axoplasm of the sciatic nerves in neuropathy induced by the long-term administration of cadmium to rats. The glycogen particles in the glycogenosomes were larger than those deposited in the intracytoplasmic matrix. Two forms of alpha-glucosidases, acid and neutral, were found in the sciatic nerve of normal rat. Cadmium ions inhibited the activity of the neutral alpha-glucosidase by a maximum of 24.0%, while acid alpha-glucosidase was not inhibited. Hg ions completely inhibited both forms of alpha-glucosidases; however, it has been reported that no glycogenosomes appear in Hg++-induced neuropathy. It was considered that the inhibitory effect of cadmium on the neutral alpha-glucosidase led to the enlargement of glycogen particles, and the large glycogen molecules were then engulfed in the lysosome system.
 ...
PMID:Mechanism of glycogenosome formation in axons of cadmium-induced neuropathy--ultrastructural and biochemical studies. 1562 22

The goal of antidiabetes therapy is to reduce glycosylated hemoglobin (HbA(1c)) levels to prevent or minimize the microvascular complications associated with this disease, such as retinopathy, nephropathy, and neuropathy. Glycemic control, defined by the American Diabetes Association (ADA) as HbA(1c) <7.0%, is often difficult to achieve despite current treatments, including oral antidiabetes agents, such as biguanides (metformin), sulfonylureas, thiazolidinediones, dipeptidyl peptidase-IV (DPP-IV) inhibitors, meglitinides, and alpha-glucosidase inhibitors, as well as injectable agents, such as glucagon-like peptide-1 (GLP-1) analogues and insulin. In addition, antidiabetes treatments often become less effective over time as insulin resistance increases and pancreatic beta-cell function deteriorates. The latest ADA guidelines also recommend a range of interventions to control the multiple coexisting conditions associated with this chronic, progressive disease, including dyslipidemia and hypertension. This review highlights the new antidiabetes drug classes, which include incretin mimetics, cannabinoid receptor type 1 antagonists, and bile acid sequestrants, and compares these agents to established treatments with regard to efficacy and tolerability. The more recently developed antidiabetes drugs have been shown in clinical trials to produce glucose-lowering effects similar to those of established antidiabetes agents. Many of the new antidiabetes agents can be safely combined with established therapies to further improve glycemic control. In addition, the new agents may provide additional significant cardiometabolic benefits, including improving the lipid profile, lowering blood pressure, and reducing body weight. These new treatments may have the potential to greatly improve the management of type 2 diabetes.
 ...
PMID:More choices than ever before: emerging therapies for type 2 diabetes. 1853 25


1 2 Next >>