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)

Human colon adenocarcinoma cells (HT29-ATCC) and the clone HT29-5F7 were cultured under conditions that differentiate cells to a polarized intestinal phenotype. Differentiated cells showed the presence of junctional complexes and intercellular lumina bordered by microvilli. Intestinal brush border hydrolase activities (sucrase, aminopeptidase N, lactase and maltase) were detected mainly in differentiated HT29-ATCC cells compared with the differentiated clone, HT29-5F7. The presence of non-GM1 receptors of Escherichia coli heat-labile enterotoxin (LT-I) on both types of differentiated HT29 cells was indicated by the inability of cholera toxin B subunit to block LT-I binding to the cells. Binding of LT-I to cells, when GM1 was blocked by the cholera toxin B subunit, was characterized by an increased number of LT-I receptors with respect to undifferentiated control cells. Moreover, both types of differentiated cells accumulated higher amounts of cyclic AMP in response to LT-I than undifferentiated cells. Helix pomatia lectin inhibited the binding of LT-I to cells and the subsequent production of cyclic AMP. LT-I recognized blood group A-active glycosphingolipids as functional receptors in both HT29 cell lines and the active pro-sucrase form of the glycoprotein carrying A-blood group activity present in HT29-ATCC cells. These results strongly suggest that LT-I can elicit an enhanced functional response using blood group A-active glycoconjugates as additional receptors on polarized intestinal epithelial cells.
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PMID:Functional interaction of Escherichia coli heat-labile enterotoxin with blood group A-active glycoconjugates from differentiated HT29 cells. 1688 90

In an attempt to prevent the complications of type 2 diabetes, particular attention should be paid to controlling postprandial glycemia (PPG): on the one hand, it contributes substantially to the HbAlc level in moderately controlled patients, on the other hand, the postprandial glucose peak induces oxidative stress and endothelial dysfunction, the first step toward accelerated atherogenesis. Metformin, glitazones, and insulin secretagogues have an additive effect on fasting blood glucose (FBG), and a significant impact on PPG. Alpha-glucosidase inhibitors can reduce PPG by a mean 0.50 g/l, no matter what the insulin resistance or insulinopenia status or the other diabetes treatments already in use. After evolving for several years and the failure of oral antidiabetics to normalize fasting blood glucose, long-acting (slow-acting) insulin analogues, well titrated, can reach this goal. They will have no effect on PPG other than a simple level effect. At this stage, rather than overtreating high fasting blood glucose concentrations, systematic PPG exploration should be the rule so as to better define PPG treatment: the advantages of alpha-glucosidase inhibitors and the role of GLP-1 analogs should be defined, the use of a rapid-acting insulin analog before the meal causing the highest postprandial blood glucose excursions, even systematically at all three meals, should be considered, or inhaled insulin. As natural life expectancy is on the rise, these active strategies designed to normalize the daily glycemic profile, necessary in a strict strategy to prevent the complications of diabetes, will need to be discussed for an increasing number of patients with type 2 diabetes.
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PMID:How should postprandial glycemia be treated? 1737 3

Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors. Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion. We compared the postprandial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism, on insulin requirement, on GLP-1 secretion, and on inflammatory and endothelial markers in viscerally obese subjects. Twenty-four viscerally obese subjects with relative insulin resistance participated in this study. Subjects were given a single dose of miglitol (50 mg), acarbose (100 mg), or placebo blindly and randomly before a meal in a crossover design. The meal loads after drug administration were tested 3 times within 2 weeks. We measured glucose, insulin, lipids, lipoprotein lipase, interleukin 6, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and active GLP-1 at before and various minutes after the meal. Single administration of both alpha-glucosidase inhibitors had several beneficial effects in improving postprandial hyperglycemia and reducing postprandial insulin requirement approximately 25% of placebo without adversely affecting lipid profiles. Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol, acarbose, and placebo administrations, miglitol significantly suppressed the increases in triglycerides, remnant-like particle triglycerides, and remnant-like particle cholesterol compared to acarbose and placebo in the early phase. Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose (P < .01) and placebo (P < .001), and significantly suppressed the postprandial increase in interleukin 6 compared to placebo (P < .01). The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects, in preference to acarbose. Further studies are needed to elucidate the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis.
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PMID:Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects. 1870 58

Alpha-glucosidase inhibitors are marketed as therapeutic drugs for diabetes that act through the inhibition of carbohydrate metabolism. Inhibitors of the alpha-glucosidases that are involved in the biosynthesis of N-linked oligosaccharide chains have been reported to have antitumor, antiviral, and apoptosis-inducing activities, and some have been used clinically. alpha-Glucosidase inhibitors have interesting biological activities, and their design, synthesis, and screening are being actively performed. In quite a few reports, however, alpha-glucosidases with different origins than the target alpha-glucosidases, have been used to evaluate inhibitory activities. There might be confusion regarding the naming of alpha-glucosidases. For example, the term alpha-glucosidase is sometimes used as a generic name for alpha-glucoside hydrolases. Moreover, IUBMB recommends the use of "alpha-glucosidase" (EC 3.2.1.20) for exo-alpha-1,4-glucosidases, which are further classified into four families based on amino acid sequence similarities. Accordingly, substrate specificity and susceptibility to inhibitors varies markedly among enzymes in the IUBMB alpha-glucosidases. The design and screening of inhibitors without consideration of these differences is not efficient. For the development of a practical inhibitor that is operational in cells, HTS using the target alpha-glucosidase and the computer-aided design of inhibitors based on enzymatic information concerning the same alpha-glucosidase are essential.
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PMID:Design and screening strategies for alpha-glucosidase inhibitors based on enzymological information. 1919 93

From 42 different hot springs in 6 provinces belonging to distinct geographical regions of Turkey, 451 thermophilic bacilli were isolated and 67 isolates with a high amylase activity were selected to determine the alpha-glucosidase production capacities by using pNPG as a substrate. Alpha-glucosidase production capacities of the isolates varied within the range from 77.18 to 0.001 U/g. Eleven of our thermophilic bacilli produced alpha-glucosidase at significant levels comparable with that of the reference strains tested, thus five strains, F84b (77.18 U/g), A333 (48.64 U/g), F84a (36.64 U/g), E134 (32.09 U/g), and A343 (10.79 U/g) were selected for further experiments. 16S rDNA sequence analysis revealed that these selected isolates all belonged to thermophilic bacilli 16S rDNA genetic group 5, four of them representing the genus Geobacillus, while strain A343 had an uncultured bacterium as the closest relative. Changes of alpha-glucosidase levels in the intracellular and extracellular fractions were determined during 48-h cultivation of A333, A343, F84a, F84b, E134, and the reference strain G. stearothermophilus ATCC 12980. According to alpha-glucosidase production type and enzyme levels in intracellular and extracellular fractions, Geobacillus spp. A333, F84a and F84b were defined as extracellular enzyme producers, whereas the thermophilic bacterium A343 was found to be an intracellular alpha-glucosidase producer, similar to ATCC 12980 strain. Geobacillus sp. E134 differed in alpha-glucosidase production type from all tested isolates and the reference strain; it was described as a membrane-associated cell-bound enzyme producer. In this study, apart from screening a great number of new thermophilic bacilli from the hot springs of Turkey, which have not yet been thoroughly studied, five new thermostable alpha-1,4-glucosidase-producing bacilli that have biotechnological potential with alpha-glucosidases located at different cell positions were obtained.
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PMID:Isolation of alpha-glucosidase-producing thermophilic bacilli from hot springs of Turkey. 1933 99

Alpha-glucosidase I regulates trimming of the terminal alpha-1,2-glucose residue in the N-glycan processing pathway, which plays an important role in quality control systems in mammalian cells. Previously, we identified the gene encoding alpha-glucosidase I in the opportunistic human fungal pathogen Aspergillus fumigatus, namely Afcwh41. Deletion of the Afcwh41 gene results in a severe reduction of conidia formation, a temperature-sensitive deficiency of cell wall integrity, and abnormalities of polar growth and septation. An upregulation of the genes encoding Rho-type GTPases was also observed, which suggests activation of the cell wall integrity pathway in the mutant. Using 2D gel analysis, we revealed that the proteins involved in protein assembly, ubiquitin-mediated degradation and actin organization are altered in the DeltaAfcwh41 mutant. Evidence was obtained for a defect in the polarized localization of the actin cytoskeleton in the mutant. Our results suggest that blocking of the glucose trimming in A. fumigatus might induce accumulation of misfolded proteins in the endoplasmic reticulum; these misfolded proteins are probably required for cell wall synthesis and thus activate the cell wall integrity pathway, which then causes the abnormal polarity associated with the DeltaAfcwh41 mutant.
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PMID:Comparative proteomic analysis of an Aspergillus fumigatus mutant deficient in glucosidase I (AfCwh41). 1938 62

In this study, we investigated structural changes in alpha-glucosidase during urea denaturation. Alpha-glucosidase was inactivated by urea in a dose-dependent manner. The inactivation was a first-order reaction with a monophase process. Urea inhibited alpha-glucosidase in a mixed-type reaction. We found that an increase in the hydrophobic surface of this enzyme induced by urea resulted in aggregation caused by unstable folding intermediates. We also simulated the docking between alpha-glucosidase and urea. The docking simulation suggested that several residues, namely THR9, TRP14, LYS15, THR287, ALA289, ASP338, SER339, and TRP340, interact with urea. Our study provides insights into the alpha-glucosidase unfolding pathway and 3D structure of alpha-glucosidase.
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PMID:Alpha-glucosidase folding during urea denaturation: enzyme kinetics and computational prediction. 1941 60

Alpha-glucosidase from Aspergillus niger is an enzyme that catalyzes hydrolysis of alpha-1,4 linkages and transglucosylation to form alpha-1,6 linkages. In this study, an analytical method of oligosaccharides by nuclear magnetic resonance (NMR) was used to provide quantitative estimation of the fractions of each sugar unit and was applied to characterize the alpha-glucosidase reaction. Our data indicated that alpha-glucosidase reacts with the nonreducing end of oligosaccharides to form an alpha-1,6 linkage, and then a sugar unit with two alpha-1,6 linkages is gradually produced. Data from mass spectrometry suggested that the sugar unit with two alpha-1,6 linkages originates mainly from a 3mer and/or 4mer when oligosaccharides are used as substrates.
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PMID:Monitoring the hydrolysis and transglycosylation activity of alpha-glucosidase from Aspergillus niger by nuclear magnetic resonance spectroscopy and mass spectrometry. 1952 54

Alpha-glucosidase enzyme is present ubiquitously throughout the lumen of the small intestine. It is responsible for the breakdown of complex into simple carbohydrates. alpha-Glucosidase inhibitors such as miglitol, are drugs that have greater affinity towards this enzyme in comparison to carbohydrates. Miglitol regulates the postprandial glucose levels directly by inhibiting the enzyme reversibly and also indirectly by including the secretion of glucagon like peptide-1 (GLP-1). The aims of this study were (i) to design a controlled release (CR) mucoadhesive (in the intestine) formulation of miglitol which would inhibit the alpha-glucosidase enzyme for a longer duration of time (in comparison to the non-controlled release (IR) formulation) thus reducing the dosing frequency, and also controlling the postprandial glucose levels more effectively over a longer period of time; (ii) to assess the effect of different formulation parameters on the release of miglitol in vitro from the CR pellets; (iii) to evaluate the mucoadhesion of pellets in the intestine ex vivo; (iv) to study the effect of formulation parameters on plasma GLP-1 levels; and (v) to find out the effect of formulations on postprandial glucose levels. The data obtained was analysed to find out whether there was a correlation between these different parameters. Four controlled release formulations (CR1, CR2, CR3 and CR4) of miglitol comprising of multilayered pellets were designed successfully. The CR4 formulation containing 30% of 20 cps of ethyl cellulose (the retarding layer of the formulation) displayed slowest release of miglitol in vitro in comparison to other formulations. We designed an ex vivo experimental setup for studying the mucoadhesion of the pellets in the lumen of the intestine. Results indicated that amongst all of the adherent pellets, 5% were found to be adhering in the duodenal region, 61% in the jejunum, 32% in the ileum and 2% in the colon. Two of the controlled release formulations CR1 and CR4 were evaluated in vivo in dogs. Both the formulations displayed significantly higher and more prolonged (greater AUC) levels of GLP-1 in comparison to either the placebo or the immediate release (IR) formulations. They even displayed a significantly better control of postprandial glucose in comparison to either placebo or IR formulations. However, a comparison between the two controlled release formulations (CR1 and CR4) revealed that the plasma GLP-1 (AUC by CR1=63.1+/-1.32 and CR4=66.2+/-0.82) and postprandial glucose values due to both the formulations were rather similar despite their differences in in vitro release as well as pharmacokinetic profiles (plasma miglitol AUC of CR1=16.17+/-4.11 and CR4=27.17+/-4.33).
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PMID:Design and evaluation of oral bioadhesive controlled release formulations of miglitol, intended for prolonged inhibition of intestinal alpha-glucosidases and enhancement of plasma glucagon like peptide-1 levels. 1956 73

Alpha-glucosidase inhibitor can reduce the postprandial hyperglycemia and have good effect on preventing and treating the diabetes and diabetic complication. Along with the application of acarbose which is a kind of alpha-glucosidase inhibitor, many research groups pay attention to the crude alpha-glucosidase inhibitor screened from the medicinal herbs in order to find new, safe, and effective medicine. The development of alpha-glucosidase inhibitor screened from the medicinal herbs and its evaluation in vivo and vitro as well as the varieties of the medicinal herbs that contain alpha-glucosidase inhibitor in recent 30 years were summarized in this paper.
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PMID:[Development of alpha-glucosidase inhibitor from medicinal herbs]. 2081 24


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