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)

ABSTRACT Iron is an essential element for biological systems. There is increasing evidence that excess iron supplementation results in the deposition of iron in the duodenum and enhances mucosal injury and cell proliferation in the colon and cecum. In the present study we examined whether chronic exposure to high levels of iron fortification affects the functional integrity of the small intestine, especially the activities of various brush border enzymes. Wistar rats were fed iron 29 mg/kg body weight (or 6.58 mg/kg Fe) daily in the form of FeSO(4).7H(2)O for 39 days. The activities of brush border alkaline phosphatase (AP) (p < 0.001), sucrase (p < 0.01), maltase (p < 0.05), lactase (p < 0.05), and trehalase (p < 0.001) were reduced in purified membranes in iron-fed animals compared to controls. However, the activities of leucine amino peptidase (LAP) and gamma-glutamyl transpeptidase (gamma-GTP) were unaffected under these conditions. Analysis of alkaline phosphatase activity across the crypt-villus unit revealed a significant decrease (p < 0.05) all across the crypt-villus length, while sucrase activity was reduced (p < 0.01) only in the midvillus axis in iron-exposed animals. Kinetic studies showed a decrease in V(max) of AP from 1.11 to 0.83 units/mg protein and for sucrase from 0.77 to 0.43 units/mg protein in iron-fed rats, with no change in the apparent K(m) of the enzymes (AP, 8 mM; sucrase, 10 mM). Western blot analysis corroborated these findings. These results indicate that chronic iron exposure alters the activities of brush border enzymes, resulting in intestinal dysfunctions.
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PMID:Effect of chronic iron ingestion on the development of brush border enzymes in rat intestine. 2002 Sep 42

The increasing proportions of older persons accounting for global populations, and the implications for increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause of concern for clinicians. Considering that older persons are a very heterogeneous group of individuals, the management of type 2 diabetes is particularly challenging. Once type 2 diabetes is diagnosed, the principles of its management are similar to those in younger patients, but with special considerations linked to the increased prevalence of comorbidities and relative inability to tolerate adverse effects of medication and hypoglycemia. In addition, there are clinical aspects complicating diabetes care in the elderly including cognitive disorders, physical disability and geriatric syndromes, such as frailty. Available anti-diabetic oral drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin) alpha-glucosidase inhibitors, thiazolidinediones (TZDs) and newly introduced glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to reach adequate metabolic control with the risk of adverse effects due to age-related changes in drug metabolism. The present review discusses the European Diabetes Working Party guidelines for type 2 diabetes in older persons with and without frailty and their importance on preventing or at least slowing down diverse aspects of disability.
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PMID:Diabetes care targets in older persons. 2011 30

Life expectancy has significantly increased over the past 30 years, with a greater prevalence of diverse disease states, especially type 2 diabetes mellitus. As older persons are a very heterogeneous group with an increased prevalence of comorbidities and a relative inability to tolerate the adverse effects of oral antidiabetic agents, the treatment of type 2 diabetes is particularly demanding. The principles of its management are similar to those in younger patients, but with special considerations linked to comorbidities and clinical status. The available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors, thiazolidinediones and newly introduced inhibitors of glucagon-like peptide 1 degrading enzyme dipeptidyl peptidase 4 (DPP-4). In addition, clinical aspects complicate diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty. The European Diabetes Working Party for Older Persons has increased glycaemic recommendations for target haemoglobin A(1c) from <7% to <or=8% in the presence of frailty. This working party updated their guidelines in 2008 and their aim is to ensure that older Europeans with type 2 diabetes have high-quality diabetes care throughout their lives. The working party has created guidelines for the use of many drugs, and we will discuss some of these guidelines on the use of oral antidiabetic agents and their importance in the presence of frailty. Furthermore, as type 2 diabetes progresses in older persons, polypharmacy intensification is usually required to reach adequate glycaemic control, with the risk of adverse effects. In particular, clinical evidence shows that the use of sulfonylureas is associated with a greater risk of hypoglycaemica, whereas metformin and alpha-glucosidase inhibitors are associated with an increased risk of adverse gastrointestinal effects. The adverse effects of the recently introduced DPP-4 inhibitors are nasopharyngitis and/or upper respiratory tract infections. The literature suggests that oral antidiabetic agents are suitable for older persons; however, underappreciated risk factors, such as cognitive decline in frail individuals, have an important impact on oral antidiabetic treatment options.
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PMID:Antidiabetic oral treatment in older people: does frailty matter? 2013 69

The increasing proportions of older persons accounting for global populations, and the implications for increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause of concern for clinicians. Considering that older persons are a very heterogeneous group of individuals, the management of type 2 diabetes is particularly challenging. Once type 2 diabetes is diagnosed, the principles of it's management are similar to those in younger patients, but with special considerations linked to the increased prevalence ofcomorbidities and relative inability to tolerate adverse effects of medication and hypoglycemia. In addition, there are clinical aspects complicating diabetes care in the elderly including cognitive disorders, physical disability and geriatric syndromes, such as frailty. Available anti-diabetic oral drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors, thiazolidinediones (TZDs) and newly introduced glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to reach adequate metabolic control with the risk of adverse effects due to age-related changes in drug metabolism. The present review discusses the European Diabetes Working Party guidelines for type 2 diabetes in older persons with and without frailty and their importance on preventing or at least slowing down diverse aspects of disability.
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PMID:Pathophysiology of diabetes in elderly people. 2051 91

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

The natural lifestyle of Aspergillus niger made them more effective secretors of hydrolytic proteins and becomes critical when this species were exploited as hosts for the commercial secretion of heterologous proteins. The protein secretion profile of A. niger and its mutant at different pH was explored using iTRAQ-based quantitative proteomics approach coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study characterized 102 highly confident unique proteins in the secretome with zero false discovery rate based on decoy strategy. The iTRAQ technique identified and relatively quantified many hydrolyzing enzymes such as cellulases, hemicellulases, glycoside hydrolases, proteases, peroxidases, and protein translocating transporter proteins during fermentation. The enzymes have potential application in lignocellulosic biomass hydrolysis for biofuel production, for example, the cellulolytic and hemicellulolytic enzymes glucan 1,4-alpha-glucosidase, alpha-glucosidase C, endoglucanase, alpha l-arabinofuranosidase, beta-mannosidase, glycosyl hydrolase; proteases such as tripeptidyl-peptidase, aspergillopepsin, and other enzymes including cytochrome c oxidase, cytochrome c oxidase, glucose oxidase were highly expressed in A. niger and its mutant secretion. In addition, specific enzyme production can be stimulated by controlling pH of the culture medium. Our results showed comprehensive unique secretory protein profile of A. niger, its regulation at different pH, and the potential application of iTRAQ-based quantitative proteomics for the microbial secretome analysis.
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PMID:Quantitative iTRAQ secretome analysis of Aspergillus niger reveals novel hydrolytic enzymes. 2054 67

In addition to the hypoglycemia and weight gain associated with many treatments for type 2 diabetes, alpha-glucosidase inhibitors, thiazolidinediones, metformin, sulfonylureas, and the glinides do not address all of the multiple defects existing in the pathophysiology of the disease. Cumulatively, these oral agents address the influx of glucose from the gastrointestinal tract, impaired insulin activity, and acute beta-cell dysfunction in type 2 diabetes; however, until recently, there were no means to deal with the inappropriate hyperglucagonemia or chronic beta-cell-decline characteristic of the disease. The recently introduced incretin-based therapies serve to address some of the challenges associated with traditionally available oral antidiabetic agents. In addition to improving beta-cell function, stimulating insulin secretion, and inhibiting glucagon secretion, these agents reduce appetite, thereby stabilizing weight and/or promoting weight loss in patients with type 2 diabetes. Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these incretin-based therapies is recommended in the treatment of type 2 diabetes, based on their overall safety and ability to achieve the glycosylated hemoglobin level goal. As such, both the American Diabetes Association and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in both treatment-naive and previously treated patients. The AACE/ACE guidelines clearly state that these agents should not be limited to third- or fourth-line therapy.
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PMID:Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting. 2080 67

Obesity is a well known risk factor for type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus are at risk for weight gain as a result of multiple influences, including sedentary lifestyle, high-calorie diet, diabetes medications, sociocultural factors, chronic medical and psychiatric illnesses, and a dysregulated enteroendocrine axis. Because both diabetes mellitus and obesity predispose patients to abnormal cardiometabolic profiles and increased cardiovascular disease, management of diabetes mellitus should focus on weight management and optimizing cardiometabolic parameters, concomitant with glycemic control. Lifestyle modification incorporating healthy, calorie-appropriate diets and increased physical activity, in addition to metformin, are central components to diabetes management and weight management. These interventions have been shown to improve body weight, glycemic control, and overall cardiometabolic profile. The weight-neutral and weight-losing diabetes medications include metformin, alpha-glucosidase inhibitors, glucagon-like peptide-1 analogs, dipeptidyl peptidase-4 inhibitors, and amylin analogs. It is essential that providers understand the metabolic and weight effects of diabetes medications in order to develop strategies for managing diabetes mellitus while helping patients maintain or lose weight in order to improve their overall health outcomes.
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PMID:Weight management in type 2 diabetes mellitus. 2096 May 55

After metformin, with insulin in patients with severe hyperglycemia, current recommendations on treatment for type 2 diabetes suggest several pharmacotherapies, including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors and others. Among them, recent data emphasize the effectiveness at a lower risk for hypoglycemia of dipeptidyl peptidase-4 inhibitors compared to other drug groups. One particular drug from this group, sitagliptin offers sound effectiveness, safety and tolerability resulting in good glycemic control at a very low risk for hypoglycemia. This review explores available evidence on the optimal treatment for type 2 diabetes regarding glycemic control with minimal risk for hypoglycemia based on evidence from clinical trials and meta-analyses within the context of the current treatment recommendations by the Spanish Society of Diabetes.
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PMID:[Hypoglycemia in the diabetes treatment - risk minimization with dipeptidyl peptidase-4 inhibitors]. 2124 Mar 32

Numerous drugs with different mechanisms of action and different pharmacologic profiles are being used with the aim of improving glycemic control in patients with type 2 diabetes. Therapeutic options for patients with type 2 diabetes and chronic kidney disease (CKD) are limited because a reduced glomerular filtration rate results in the accumulation of certain drugs and/or their metabolites. Conventional oral hypoglycemic agents, such as sulfonylurea (SU), are not suitable due to the risk of prolonged hypoglycemia; furthermore, metformin is contraindicated for moderate to advanced CKD. Therefore, in order to achieve good glycemic control, insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy. However, some agents have been used even in patients with CKD. Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands. They are rarely accompanied by hypoglycemia, and are attractive therapeutic options even in the dialysis population. In addition, alpha-glucosidase inhibitors are rarely accompanied by hypoglycemia and are administered without dose adjustments in dialysis patients. However, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended that alpha-glucosidase inhibitors should be avoided in patients with advanced stage CKD and on dialysis. Furthermore, mitiglinide is not currently used in the US. Thus, recommended oral antidiabetic agents differ between countries. Moreover, dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents, which may be used more frequently in the future in patients with type 2 diabetes and CKD. Here, we describe the pharmacokinetics, metabolism, clinical efficacy, and safety of oral Antidiabetic agents for patients with CKD, including those receiving dialysis.
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PMID:Antidiabetic agents in patients with chronic kidney disease and end-stage renal disease on dialysis: metabolism and clinical practice. 2130 32


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