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)

Previously, we constructed a gene disruption in the pullulanase I gene of Bacteroides thetaiotaomicron 5482A. This mutant, designated B. thetaiotaomicron 95-1, had a lower level of pullulanase specific activity than did wild-type B. thetaiotaomicron but still exhibited a substantial amount of pullulanase activity. Characterization of the remaining pullulanase activity present in B. thetaiotaomicron 95-1 has identified an alpha(1----4)-D-glucosidic bond cleaving pullulanase which has been tentatively designated a neopullulanase. The neopullulanase (pullulanase II) is a 70-kDa soluble protein which cleaves alpha(1----4)-D-glucosidic bonds in pullulan to produce panose. The neopullulanase also cleaved alpha(1----4) bonds in amylose and in oligosaccharides of maltotriose through maltoheptaose in chain length. An alpha-glucosidase from B. thetaiotaomicron 95-1 was characterized. The alpha-glucosidase was partially purified to a preparation containing three proteins of 80, 57, and 50 kDa. Pullulan and amylose were not hydrolyzed by the alpha-glucosidase. alpha(1----4)-D-Glucosidic oligosaccharides from maltose to maltoheptaose were hydrolyzed to glucose by the alpha-glucosidase. The alpha-glucosidase also hydrolyzed alpha(1----6)-linked oligosaccharides such as panose (the product of the pullulanase II action on pullulan) and isomaltotriose.
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PMID:Characterization of a neopullulanase and an alpha-glucosidase from Bacteroides thetaiotaomicron 95-1. 170 85

The trypanocidal drug suramin is known to concentrate in lysosomes and to depress the activity of different lysosomal enzymes. We have previously shown that suramin can inhibit the activity of the islet lysosomal enzyme acid amyloglucosidase, a glycogenolytic glucose-producing hydrolase, which seems to be involved in certain insulin-secretory processes. In the present investigation we studied the pH dependency and dose-response effects of suramin on islet lysosomal enzyme activities as well as the effect of suramin treatment on the insulin-secretory response to various secretagogues in mice. It was found that two injections of suramin (0.18 mmol/kg) to normal NMRI mice at -24 and -2 h induced a moderate depression of the activities of islet acid amyloglucosidase (-22%) and acid phosphatase (-13%), whereas no effect was recorded for the activities of acid alpha-glucosidase, N-acetyl-beta-D-glucosaminidase and the non-lysosomal enzyme neutral alpha-glucosidase. Direct addition of different concentrations of suramin to islet homogenates showed that the drug was a potent inhibitor of acid amyloglucosidase and acid alpha-glucosidase at pH 4.0. At pH 5.0, suramin induced a large increase in acid alpha-glucosidase activity, whereas acid amyloglucosidase and acid phosphatase were inhibited. Suramin-injected mice showed a reduced insulin-secretory response to the sulphonylurea drug glibenclamide (-45%), whereas the insulin response to the cholinergic agonist carbachol or the phosphodiesterase inhibitor IBMX (1-isobutyl-3-methylxanthine) was unaffected. It is concluded that suramin inhibits islet acid amyloglucosidase activity in vivo and in vitro, whereas its effect on acid alpha-glucosidase is complex and pH dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the lysosomotropic drug suramin on islet lysosomal enzyme activities and the insulin-secretory response induced by various secretagogues. 172 7

Starch digestion and absorption is augmented appreciably by physical processing of grain or legume and by heating to 100 degrees C for several minutes before its ingestion. Starch, a polysaccharide composed of alpha 1,4-linked glucose units (amylose) and alpha 1,4-1,6-linked branched structure (amylopectin), is cleaved in the duodenal cavity by secreted pancreatic alpha-amylase to a disaccharide (maltose), trisaccharide (maltotriose), and branched alpha-dextrins. These final oligosaccharides are hydrolyzed efficiently by complimentary action of three integral brush border enzymes at the intestinal surface: glucoamylase (maltase-glucoamylase, amyloglucosidase), sucrase (maltase-sucrase) and alpha-dextrinase (isomaltase). The final monosaccharide glucose product is then cotransported into the enterocyte along with Na+ by a specific brush border 75-kDa transport protein in the rate-limiting step for overall starch assimilation. By virtue of this sequential luminal and membrane digestion followed by glucose transport, starch is assimilated in a very efficient manner in nonruminants.
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PMID:Starch digestion and absorption in nonruminants. 172 68

Mechanisms for the assimilation of glucose polymers have been inferred from perfusion studies. To further define these mechanisms, the results of measurements of unidirectional glucose fluxes across short-circuited rabbit jejunal segments in vitro are reported. Glucose polymer-stimulated short-circuit current was similar to that of glucose [19 +/- 6.0 microA/cm2 (n = 7) and 26 +/- 5.7 microA/cm2 (n = 13), respectively] and was inhibited by both acarbose and phlorizin. Acarbose, an alpha-glucosidase inhibitor with no effects of glucose transport, was used to uncouple digestion from absorption. Mucosal-to-serosal flux of glucose polymer-derived glucose was lower than that of an equal weight/volume of glucose [124 +/- 62 nmol.h-1.cm-2 (n = 4) vs. 452 +/- 121 nmol.h-1.cm-2 (n = 6); P less than 0.05] and was inhibited by both phlorizin and acarbose. No glucose polymers were detected in the serosal bath solutions by thin-layer chromatography. It is concluded that glucose polymer-derived glucose is transported by a phlorizin-inhibitable process at a rate slower than that of free glucose, a finding that suggests that hydrolysis limits glucose polymer assimilation.
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PMID:Transport of glucose polymer-derived glucose by rabbit jejunum. 173 15

We examined GLUT-4 glucose transporter protein and mRNA in muscle tissue from a new rodent model of non-insulin-dependent diabetes mellitus (NIDDM), the male obese Zucker diabetic fatty (ZDF) rat [ZDF/Drt-fa(F10)]. We also determined whether prevention of hyperglycemia might affect GLUT-4 expression by feeding the intestinal alpha-glucosidase inhibitor acarbose (40 mg/100 g diet) in the diet of male ZDF rats for 19 wk, starting at least 1 wk before the onset of diabetes. Fasting glucose was four- to sixfold greater in diabetic ZDF rats (24.1 +/- 6.7 mM) compared with lean or obese nondiabetic rats. Fasting insulin in diabetic ZDF rats (0.5 +/- 0.1 ng/ml) was similar to lean rats (0.4 +/- 0.1) but greatly reduced compared with obese nondiabetic rats (18.7 +/- 4.0 ng/ml). Acarbose treatment significantly reduced fasting glucose levels to 13.4 +/- 1.4 mM, while insulin levels increased to 1.6 +/- 0.3 ng/ml. GLUT-4 protein levels in diabetic ZDF rats were reduced approximately 40% in red quadriceps and mixed gastrocnemius muscles but were unchanged in white quadriceps muscle. Acarbose treatment was associated with a twofold increase in GLUT-4 protein and mRNA in mixed gastrocnemius muscle. These data indicate that, in this obese model of NIDDM without hyperinsulinemia, there is reduced muscle GLUT-4 protein in red but not white muscle fiber types. The decrease in muscle GLUT-4 expression in this model of NIDDM can be prevented by acarbose treatment, which reduces hyperglycemia and increases beta-cell responsiveness.
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PMID:Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa). 176 39

The alpha-glucosidase inhibitor acarbose induces a reversible delay of carbohydrate digestion. This action represents a new therapeutic option for the treatment of diabetes mellitus. The current investigation is a prospective, randomized double-blind crossover trial in 24 non-insulin dependent diabetics, fairly well controlled on diet alone or diet plus sulphonylurea. In periods of 10 weeks, the patients received successive treatment with acarbose and placebo in random order. A significantly lower HbA1 level and urinary glucose excretion were shown during acarbose as compared to placebo. The other parameters of diabetic control remained unchanged. Acarbose induced no significant alterations in the concentrations of important electrolytes, iron, vitamin B12 and folic acid. Although no major side effects occurred, meteorism and flatulence were frequent complaints. These data suggest that acarbose, in a dosage of 3 x 100 mg/day, is a safe drug, with slight beneficial effect on diabetic metabolic control.
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PMID:Effects of acarbose on carbohydrate metabolism, electrolytes, minerals and vitamins in fairly well-controlled non-insulin-dependent diabetes mellitus. 177 45

To clarify the enzyme participates in maltotriose synthesis, we purified maltase from rabbit kidney using 2-amino-2-hydroxymethylpropane-1,3-diol (Tris) affinity column chromatography. The purified enzyme possessed specific activity of 33.7 mumol/mg/min and estimated molecular weight of 350,000 dalton, as judged by SDS-polyacrylamide gel electrophoresis, comparable with those reported from rat kidney. Moreover this enzyme possessed not only maltase (maltose----glucose) but also amylomaltase (maltose----maltotriose) activity, and both activities were inhibited by Tris in a dose-dependent manner with similar IC50 values. From these results, we concluded that maltotriose was synthesized by maltase in vitro and that kidney maltase may participate in sugar metabolism in vivo.
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PMID:Synthesis of maltotriose by maltase purified from rabbit kidney. 177 60

In two randomized, placebo-controlled, double-blind studies, the efficacy, duration of action and tolerability of a single morning dose of 25, 50, and 100 mg miglitol (BAY m 1099), an absorbable inhibitor of intestinal alpha-glucosidases, were assessed after repetitive sucrose or maize-starch loads (50 g of carbohydrates in 400 ml of water each at 08.00, 12.00, and 17.00 h). With sucrose, miglitol reduced the postprandial rise in blood glucose, serum insulin and serum gastric inhibitory polypeptide concentrations at any dosage. This effect was dose-dependent and confined to the first carbohydrate load in the morning, thus indicating the duration of alpha-glucosidase inhibition of less than 4 h. Sucrose malabsorption, indicated by breath hydrogen responses, occurred dose-dependently with 50 and 100 mg, but not with 25 mg of miglitol. Similarly, symptoms of carbohydrate malabsorption were absent with 25 mg of the inhibitor and mild to moderate after 50 and 100 mg of miglitol. With starch as the substrate, BAY m 1099 led to a significant amelioration of glycemic and hormonal rises after the first meal, but not thereafter. A numerical dose dependency was recognized, but this was not significant at the 5% level. Symptoms of carbohydrate malabsorption were absent with 25 mg and negligible with 50 mg BAY m 1099, but occurred almost regularly with the 100-mg dose. Breath hydrogen concentrations increased gradually with the dose of miglitol administered. A single morning dose of 25-100 mg of miglitol thus may be useful for the control of postprandial hyperglycemia after breakfast. Due to the duration of action of less than 4 h, this substance should be given with the three main meals.
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PMID:Inhibition of glycemic and hormonal responses after repetitive sucrose and starch loads by different doses of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in man. 178 28

The absorbable deoxynojirimycin derivative emiglitate (BAY o 1248) is a potent competitive inhibitor of small intestinal alpha-glucosidases in man. In two similar randomized, placebo-controlled, double blind investigations, the efficacy, duration of action and tolerability of single doses of 10, 20 and 40 mg emiglitate have been assessed in healthy male volunteers after repeated sucrose or maize-starch loads at 08.00, 12.00 and 17.00 h. Even at the lowest dose used, emiglitate almost abolished the glycaemic (-88%) and hormonal responses after the first sucrose meal, simultaneously evoking significant hydrogen evolution (mean peak H2-concentration greater than 100 ppm), which was not related to the dose, and which induced unacceptable symptoms of carbohydrate malabsorption, i.e. at the dosages tested, the inhibition of glycaemic and hormonal responses was at the expense of intolerable gastrointestinal adverse effects. Flattening of postprandial responses of blood glucose, serum insulin and gastric inhibitory polypeptide was still apparent after a second sucrose load 4 h later, demonstrating long-lasting inhibition of alpha-glucosidase activity. After starch, the dose dependency of inhibition emerged more clearly than after sucrose, i.e. the reduction was less pronounced. However, emiglitate led to significant reduction of the glycaemic and hormonal rises after both the first and second starch meals. Symptoms of carbohydrate malabsorption were absent after 10 mg and were negligible with 20 mg or 40 mg emiglitate. Breath hydrogen concentration increased gradually, indicating slight but significant carbohydrate malabsorption after the highest dose of the alpha-glucosidase inhibitor. The results show that a single morning dose of 20-40 mg emiglitate might be useful in the control of postprandial hyperglycaemia after breakfast and lunch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of sucrose- and starch-induced glycaemic and hormonal responses by the alpha-glucosidase inhibitor emiglitate (BAY o 1248) in healthy volunteers. 181 67

Post-prandial glucose excursions remain elevated in most patients with diabetes even when normal fasting plasma glucose levels have been achieved. In 39 patients with type 2 diabetes who had attained basal normoglycaemia by therapy with diet alone, a sulphonylurea, a basal insulin supplement or basal plus prandial insulin the mean glycosylated haemoglobin (HbA1) values were at the upper end (mean +/- 1SD, 8.1 +/- 1.1%) of the normal range (5.0-8.2%). Miglitol, an alpha-glucosidase inhibitor, given in a dose of 50 mg three times a day was studied in a double blind randomized crossover study. In diet and sulphonylurea treated patients, a mean 25% reduction of the post-prandial plasma glucose excursions was obtained whereas in ultralente treated patients miglitol appeared to reduce basal plasma glucose levels (p < 0.006). Side effects were limited to minor gastrointestinal disturbances, usually ameliorating after the first week of therapy. Alpha-glucosidase inhibition to prevent post-prandial glycaemia may have a role in patients in whom sulphonylurea or diet therapy has been used to obtain normal basal glucose concentrations.
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PMID:Post-prandial glycaemic reduction by an alpha-glucosidase inhibitor in type 2 diabetic patients with therapeutically attained basal normoglycaemia. 184 49


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