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)

The expression of small intestinal hydrolases associated with the enterocyte brush border membrane was studied in human colon cancers and foetal colons, by means of monoclonal antibodies against human small intestinal sucrase-isomaltase (SI), maltase-glucoamylase (MGA), lactase (L), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPP-IV). The enzymes were visualized by indirect immunofluorescence on cryostat sections of tumors developed in nude mice with 6 human colon carcinoma cell lines (HT-29, Caco-2, SW-480, HRT-18, HCT-8R, and Co-115), of 27 primary colorectal carcinomas from patients, and of human foetal (16 to 20 weeks of gestation) and normal adult small intestines and colons. All 5 monoclonals bound to the brush border of the adult small intestine, but not to that of the adult colon mucosa. Antibodies against SI, APN and DPP-IV also bound to the brush border of the foetal colons, to apical borders in HT-29 and Caco-2 tumors in nude mice, and to brush border-like structures in 7/27 tumors from patients. No binding was observed for MGA and L in either tumors or foetal colons. Binding of anti-SI antibodies to the brush border of the juxta-tumoral mucosal epithelium was observed in 9/11 samples tested. These data indicate that some colon tumors exhibit a typical pattern of enterocytic differentiation which is of foetal type and which involves at least 3 brush border membrane hydrolases. Monoclonal antibodies to small intestinal hydrolases may, therefore, be important tools for identification and characterization of some differentiated colonic tumors.
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PMID:Immunohistological evidence, obtained with monoclonal antibodies, of small intestinal brush border hydrolases in human colon cancers and foetal colons. 638 73

Long-term type 2 diabetes can lead to numerous biological complications, such as hypertension and cardio-vascular disease. Key enzymes involved in the enzymatic breakdown of complex carbohydrates,pancreatic alpha-amylase and intestinal alpha-glucosidase, have been targeted as potential avenues for modulation of type 2 diabetes-associated post-prandial hyperglycemia through mild inhibition of their enzymatic activities so as to decrease meal-derived glucose absorption. Further, inhibition of hypertension-linked angiotensin I-converting enzyme (ACE) was targeted as a potential approach for modulation of diabetes-linked hypertension. Water-soluble extracts of soybean optimized for phenolic content via sprouting or bioprocessing by dietary fungus (Rhizopus oligosporus, Lentinus edodes) were investigated for inhibitory activity against porcine pancreatic alpha-amylase (PPA), yeast alpha-glucosidase, and rabbit lung ACE in vitro. PPA was allowed to react with each phenolic-optimized extract and the derivatized enzyme-phytochemical mixtures obtained were characterized for residual amylase activity. Alpha-glucosidase and ACE activities were determined in the presence of each phenolic-optimized extract. All of the soybean extracts possessed marked anti-amylase activity, with extracts of R. oligosporus-bioprocessed soybean having the strongest inhibitory activity, but only slight anti-glucosidase activity. The anti-amylase activity of each extract seemed associated with extract antioxidant activity. Anti-enzyme activity was slightly associated with total soluble phenolic content per se, but seemed more associated to the length of sprouting or bioprocessing of the soybean substrate. Short-term sprouting or bioprocessing seemed to improve anti-amylase activity, while long-term sprouting or bioprocessing seemed to aid anti-glucosidase activity. While ACE activity was strongly inhibited by all of the soybean extracts (44-97%), only sprouting was found to increase this inhibition and bioprocessing of soybean with L. edodes decreased inhibitory activity of soybean extract. The results suggest that sprouting and dietary fungal bioprocessing of soybean improve the anti-diabetic potential of soybean extracts, potentially through modulation of the phenolic profile of the extract, and further suggest that enzyme inhibitory activity may be linked to phenolic antioxidant mobilization during spouting and/ or bioprocessing. The significance of food-grade, plant-based enzyme inhibitors for modulation of carbohydrate breakdown and control of glycemic index of foods in the context of preventing hyperglycemia and diabetes mellitus complications such as hypertension in the long-term is hypothesized and discussed.
Asia Pac J Clin Nutr 2005
PMID:Anti-diabetic and anti-hypertensive potential of sprouted and solid-state bioprocessed soybean. 1592 31

In the current study, we screened 7 clonal lines from single seed phenotypes of Lamiaceae family for the inhibition of alpha-amylase, alpha-glucosidase and angiotensin converting enzyme (ACE) inhibitory activity. Water extracts of oregano had the highest alpha-glucosidase inhibition activity (93.7%), followed by chocolate mint (85.9%) and lemon balm (83.9%). Sage (78.4 %), and three different clonal lines of rosemary: rosemary LA (71.4%), rosemary 6 (68.4%) and rosemary K-2 (67.8%) also showed significant alpha-glucosidase inhibitory activity. The alpha-glucosidase inhibitory activity of the extracts was compared to selected specific phenolics detected in the extracts using HPLC. Catechin had the highest alpha-glucosidase inhibitiory activity (99.6 %) followed by caffeic acid (91.3 %), rosmarinic acid (85.1%) and resveratrol (71.1 %). Catechol (64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity. Results suggested that alpha-glucosidase inhibitory activity of the clonal extracts correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. The clonal extracts of the herbs and standard phenolics tested in this study did not have any effect on the alpha-amylase activity. We also investigated the ability of the clonal extracts to inhibit rabbit lung angiotensin I-converting enzyme (ACE). The water extracts of rosemary, rosemary LA had the highest ACE inhibitory activity (90.5%), followed by lemon balm (81.9%) and oregano (37.4 %). Lower levels of ACE inhibition were observed with ethanol extracts of oregano (18.5 %) and lemon balm (0.5 %). Among the standard phenolics only resveratrol (24.1 %), hydroxybenzoic acid (19.3 %) and coumaric acid (2.3 %) had ACE inhibitory activity.
Asia Pac J Clin Nutr 2006
PMID:Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension. 1650 Aug 86

In the current study, we investigated 2 species of the genus Rhodiola for the inhibition of alpha-amylase,alpha-glucosidase and angiotensin converting enzyme (ACE) inhibitory activity. Water extracts of Rhodiola crenulata had the highest alpha-amylase inhibitory activity (IC50,98.1 microg total phenolic /ml) followed by ethanol extract of R.crenulata (IC50, 120.9 microg total phenolic/ml) and ethanol extract of R.rosea (IC50, 173.4 microg total phenolic /ml). Ethanol R.rosea (IC50, 44.7 microg total phenolic/ml), water extract of R.rosea (IC50, 52.3 microg total phenolic/ml), water extract of R.crenulata (IC50, 60.3 microg total phenolic /ml) and ethanol extract of R.crenulata (IC50, 60.2 microg total phenolic/ml) also showed significant alpha-glucosidase inhibitory activity. The alpha-glucosidase inhibitory activity of the extracts was compared to standard tyrosol, which was significantly detected in the extracts using HPLC. Tyrosol had strong alpha-glucosidase inhibitory activity (IC50, 70.8 microg total phenolic/ml) but did not have any inhibitory effect on the alpha-amylase activity. Results suggested that alpha-glucosidase inhibitory activities of both Rhodiola extracts correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. The ability of the above Rhodiola extracts to inhibit rabbit lung angiotensin I-converting enzyme (ACE) was investigated. The ethanol extracts of R.rosea had the highest ACE inhibitory activity (38.5 %) followed by water extract of R.rosea (36.2 %) and R.crenulata (15.4 %).
Asia Pac J Clin Nutr 2006
PMID:Evaluation of Rhodiola crenulata and Rhodiola rosea for management of type II diabetes and hypertension. 1683 37

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.
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PMID:Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice. 1748 17

Type II diabetes is a heterogeneous disease where environment and genetics are important factors for the expression of the disease. The high cost for treating complications of diabetes is a burden for public health systems and governments worldwide. Type II diabetes has been causing debilitation worldwide for many decades, and a single drug that safely treats the disease has yet to be discovered. Sulfonylureas, biguanides, alpha-glucosidase, meglitinides, DPP-4 inhibitors and thiazolidinediones are among the classes of oral hypoglycemic drugs available to treat Type II diabetes, but concerns exist regarding safety and efficacy of these drugs. In this article we present the pros and cons of the six classes and discuss some of the latest advances towards the development of new drugs for the treatment of Type II diabetes.
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PMID:Type 2 diabetes and oral antihyperglycemic drugs. 1822 Jul 63

The increasing proportion of elderly persons in the global population, and the implications of this trend in terms of increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause for concern for clinicians and healthcare policy makers. The diagnosis and treatment of type 2 diabetes in the elderly is challenging, as age-related changes alter the clinical presentation of diabetic symptoms. 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 co-morbidities and relative inability to tolerate the adverse effects of medication and hypoglycaemia. In addition, there are many underappreciated factors complicating diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty, urinary incontinence and pain. Available oral antihyperglycaemic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors and thiazolidinediones. Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to achieve adequate glycaemic control with the attendant increased risk of adverse effects as a result of age-related changes in drug metabolism. The recent introduction of the incretins, a group of intestinal peptides that enhance insulin secretion after ingestion of food, as novel oral antihyperglycaemic treatments may prove significant in older persons. The two main categories of incretin therapy currently available are: glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). The present review discusses the effect of aging on metabolic control in elderly patients with type 2 diabetes, the current treatments used to treat this population and some of the more recent advances in the field of geriatric type 2 diabetes. In particular, we highlight the efficacy and safety of GLP-1 and DPP-4 inhibitors, administered as monotherapy or in combination with other oral antihyperglycaemic agents, especially when the relevant clinical trials included older persons. There is strong evidence that use of incretin therapy, in particular, the DPP-4 inhibitors, could offer significant advantages in older persons. Clinical evidence suggests that the DPP-4 inhibitors vildagliptin and sitagliptin are particularly suitable for frail and debilitated elderly patients because of their excellent tolerability profiles. Importantly, these agents lack the gastrointestinal effects seen with metformin and alpha-glucosidase inhibitors taken alone, and have a low risk of the hypoglycaemic events commonly seen with agents that directly lower blood glucose levels.
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PMID:New approaches to treating type 2 diabetes mellitus in the elderly: role of incretin therapies. 1894 59

Administration of an alpha-glucosidase inhibitor, voglibose, increases the secretion of glucagon-like peptide (GLP)-1, a key modulator of pancreatic islet hormone secretion and glucose homeostasis. In the present study, novel mechanisms by which voglibose increases active GLP-1 circulation were evaluated. Voglibose (0.001 and 0.005%) was administered in the diet to ob/ob mice for 1 day or 3 to 4 weeks to determine effects on incretin profiles and plasma activity of dipeptidyl peptidase-4 (DPP-4), an enzyme responsible for GLP-1 degradation. Voglibose showed no direct inhibitory effect against DPP-4 in vitro (DPP-4 inhibitor alogliptin, IC(50) < 10 nM). Likewise, 1-day treatment with voglibose did not change plasma DPP-4 activity; however, it increased plasma active GLP-1 by 1.6- to 3.4-fold. After chronic treatment, voglibose stimulated GLP-1 secretion, as evidenced by the 1.3- to 1.5-fold increase in plasma active plus inactive amidated GLP-1 levels. Plasma DPP-4 activity was decreased unexpectedly by 40 to 51%, resulting from reduced plasma DPP-4 concentrations in voglibose-treated mice. Voglibose increased GLP-1 content by 1.5- to 1.6-fold and 1.4- to 1.6-fold in the lower intestine and colon, respectively. The increased GLP-1 content in the colon was associated with elevated expression of gut glucagon gene. Chronic treatment with voglibose resulted in 1.9- to 4.1-fold increase in active GLP-1 circulation, which was higher than 1-day treatment. A similar treatment with pioglitazone (0.03%), an insulin sensitizer, did not affect plasma DPP-4 activity or GLP-1 levels. These results suggest that increased GLP-1 secretion, decreased DPP-4 activity, and increased gut GLP-1 content may have contributed to increased active GLP-1 circulation after chronic treatment with voglibose in a glucose control-independent manner in ob/ob mice.
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PMID:Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice. 1920 98

Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD). Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM. Summarizing the present information it can be stated that 1. Four out the five classical oral antidiabetic drug groups present proven or potential cardiac hazards; 2. These hazards are not mere 'side effects', but biochemical phenomena which are deeply rooted in the drugs' mechanism of action; 3. Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4. Glitazones should be avoided in patients with overt heart failure; 5, The novel incretin mimetic drugs and DPP-4 inhibitors--while usually inadequate as monotherapy--appear to be satisfactory adjuvant drugs due to the lack of known undesirable cardiovascular effects; 6. Customized antihyperglycemic pharmacological approaches should be implemented for the achievement of optimal treatment of T2DM patients with heart disease. In this context, it should be carefully taken into consideration whether the leading clinical status is CAD or heart failure.
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PMID:A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease. 1961 27

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


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