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)

In previous in-vivo studies we have presented indirect evidence for the involvement of islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a lysosomal glycogen-hydrolysing enzyme, in certain insulin secretory processes. In the present combined in-vitro and in-vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity were related to the insulin secretory response induced by two mechanistically different secretagogues, glucose and isobutylmethylxanthine (IBMX). It was observed that addition of the selective alpha-glucosidehydrolase inhibitor emiglitate (1 mmol/l) to isolated pancreatic islets resulted in a marked reduction of glucose-induced insulin release. This was accompanied by a pronounced suppression of islet activities of acid amyloglucosidase and acid alpha-glucosidase, whereas other lysosomal enzyme activities, such as acid phosphatase and N-acetyl-beta-D-glucosaminidase, were unaffected. Furthermore, islets first incubated with emiglitate in the presence of high (16.7 mmol/l) glucose released less insulin than untreated controls in response to glucose in a second incubation period in the absence of emiglitate. In contrast, IBMX-induced insulin release was not influenced by emiglitate although accompanied by a marked reduction of islet activities of all three alpha-glucosidehydrolases. Basal insulin secretion (1 mmol glucose/l) was unaffected in the presence of emiglitate. In-vivo pretreatment of mice with highly purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, resulted in a greatly enhanced insulin secretory response to an i.v. glucose load. The increase in insulin release was accompanied by a markedly improved glucose tolerance curve in these animals. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after an i.v. injection of IBMX. The data lend further support to our hypothesis that islet acid amyloglucosidase is involved in the multifactorial insulin secretory processes induced by glucose but not in those involving direct activation of the cyclic AMP system. The results also indicate separate, or at least partially separate, pathways for insulin release induced by glucose and IBMX.
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PMID:Islet glucan-1,4-alpha-glucosidase: differential influence on insulin secretion induced by glucose and isobutylmethylxanthine in mice. 750 86

The pseudotetrasaccharide acarbose, previously known as a potent inhibitor of intestinal alpha-glucoside hydrolases, was investigated with regard to its influence on islet lysosomal enzyme activities and the insulin secretory processes. We observed that acarbose was a potent inhibitor of mouse islet lysosomal acid glucan-1,4-alpha-glucosidase activity, EC50 approximately 5 mumol/l, as well as of acid alpha-glucosidase activity. In contrast, acarbose did not influence other lysosomal enzyme activities such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. Neutral alpha-glucosidase (endoplasmic reticulum) was only moderately inhibited in homogenate and was unaffected in intact islets. Incubation of isolated mouse islets with acarbose revealed that the pseudotetrasaccharide was a strong inhibitor of glucose-induced insulin secretion, EC50 approximately 500 nmol/l, and a significant inhibition was already observed at a concentration of acarbose as low as 100 nmol/l. The acarbose analogue maltotetrose did not influence either glucose-induced insulin release or islet lysosomal enzyme activities. Further, acarbose as well as two other alpha-glucoside hydrolase inhibitors, the deoxynojirimycin derivatives miglitol and emiglitate, did not affect islet glucose oxidation at low or high glucose levels. Acarbose also inhibited insulin release induced by the sulfonylurea glibenclamide, whereas insulin secretion stimulated by the cholinergic muscarinic agonist carbachol or the phosphodiesterase inhibitor isobutylmethylxanthine was unaffected by the drug. Moreover, complementary in vivo experiments showed that pretreatment of mice with acarbose to allow for endocytosis of the compound markedly suppressed the insulin secretory response to an intravenous glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pseudotetrasaccharide acarbose inhibits pancreatic islet glucan-1,4-alpha-glucosidase activity in parallel with a suppressive action on glucose-induced insulin release. 778 51

We have previously presented indirect in vivo evidence for the involvement of islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a lysosomal glucose-producing enzyme, in certain insulin secretory processes. In the present in vitro and in vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity would be related to the insulin secretory response induced by two mechanistically different secretagogues, the sulphonylurea derivative, glibenclamide and the acetylcholine receptor agonist, carbachol. It was observed that the selective alpha-glucosidehydrolase inhibitors emiglitate and acarbose markedly reduced glibenclamide-induced insulin release from isolated islets. Insulin release stimulated by carbachol or the protein kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate), was not inhibited. Basal insulin secretion was unaffected by emiglitate and acarbose. Further, pretreatment of mice with emiglitate resulted in a marked reduction of the in vivo insulin response to glibenclamide. Moreover, in vivo pretreatment with purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, greatly enhanced the insulin response to i.v. glibenclamide. This insulin release was accompanied by a marked depression of the blood glucose levels. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after carbachol. The data strongly suggest that islet acid amyloglucosidase is involved in the insulin secretory processes induced by glibenclamide but not in those involving stimulation of muscarinic receptors or direct activation of protein kinase C. The results also indicate separate or at least partially separate pathways for insulin release induced by glibenclamide and cholinergic stimulation.
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PMID:Changes in islet glucan-1,4-alpha-glucosidase activity modulate sulphonylurea-induced but not cholinergic insulin secretion. 827 68

Oolong tea extract (OTE) was found to inhibit the water-insoluble glucan-synthesizing enzyme, glucosyltransferase I (GTase-I), of Streptococcus sobrinus 6715. The GTase-inhibitory substance in the OTE was purified successive adsorption chromatography on Diaion HP-21 and HP-20 columns; this was followed by further purification by Sephadex LH-20 column chromatography. A major fraction that inhibited GTase activity (fraction OTF10) was obtained, and the chemical analysis of OTF10 indicated that it was a novel polymeric polyphenol compound that had a molecular weight of approximately 2,000 and differed from other tea polyphenols. Catechins and all other low-molecular-weight polyphenols except theaflavin derived from balck tea did not show significant GTase-inhibitory activities. It was found that OTE amd PTF10 markedly inhibit GTase-I and yeast alpha-glucosidase, but not salivary alpha-amylase. Various GTases purified from S. sobrinus and Streptococcus mutans were examined for inhibition by OTE and OTF10. It was determined that S. sobrinus GTase-I and S. mutans cell-free GTase synthesizing water-soluble glucan were most susceptible to the inhibitory action of OTF10, while S. sobrinus GTase-Sa and S. mutans cell-associated GTase were moderately inhibited; no inhibition of S. sobrinus GTase-Sb was observed. Inhibition of a specific GTase or specific GTases of mutants streptococci resulted in decreased adherence of the growing cells of these organisms. The inhibitory effect of OTF10 on cellular adherence was significantly stronger than that of OTE.
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PMID:Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci. 848 34

Little attention has been paid to a possible relationship between lysosomal function and stimulation of secretory processes in endocrine cells. The last few years it has become increasingly evident that the secretion of insulin from the pancreatic beta-cell is the result of a very complex cascade of events, the details of which are far from elucidated and indeed may include the participation of the lysosomal system. We report here, with a combined in vitro and in vivo approach, that selective inhibition of islet lysosomal glycogenolytic acid glucan-1,4-alpha-glucosidase activity by the long-acting 1-deoxynojirimycin derivative emiglitate induces a profound suppression of nutrient-induced insulin release. In islet homogenate emiglitate strongly and dose-dependently inhibited the activity of acid glucan-1,4-alpha-glucosidase (EC50 approximately 10(-6) M) without affecting other classical lysosomal enzyme activities. The emiglitate-induced inhibition curve for glucose-stimulated insulin secretion from isolated islets was remarkably similar to the inhibition curve for acid glucan-1,4-alpha-glucosidase. Moreover, insulin release stimulated by the nonglucose nutrient secretagogues, leucine, and alpha-ketoisocaproic acid (KIC) was totally suppressed by emiglitate. In contrast, receptor activated insulin secretion induced by the insulinotropic hormone cholecystokinin (CCK-8) was unaffected by the drug. Further, parenteral pretreatment of mice with emiglitate markedly suppressed the insulin secretory response to an iv injection of glucose or KIC, whereas the response to an iv injection of CCK-8 was unaffected. In accordance with this, islets isolated from emiglitate-treated mice showed a reduced activity of acid glucan-1,4-alpha-glucosidase and, moreover, such islets incubated in vitro, secreted less insulin in response to glucose than did control islets. Finally, pretreatment of mice with purified fungal acid glucan-1,4-alpha-glucosidase, enzyme replacement, brought about a markedly increased insulin secretory response after an iv injection of KIC, whereas the insulin response after CCK-8 injection was unaffected. Taken together with previous observations, the present data strongly suggest that islet lysosomal acid alpha-glucosidehydrolases are involved in the multifactorial process of nutrient-induced insulin secretion. The existence of hitherto unresolved and complex interactions between different beta-cell organelles in the insulin secretory processes should be thoroughly reevaluated.
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PMID:Islet acid glucan-1,4-alpha-glucosidase: a putative key enzyme in nutrient-stimulated insulin secretion. 862 92

Glycosyl-trehaloses with an isomaltosyl residue were synthesized by alpha-glucosidase from Aspergillus niger by using maltotetraose as a glucosyl donor and trehalose as the acceptor. The one trisaccharide and two tetrasaccharides formed were isolated by successive column chromatography. The results of an enzymatic digestion, methylation analysis, and 13C-NMR studies indicated that these oligosaccharides were alpha-isomaltosyl alpha-glucoside, alpha-isomaltotriosyl alpha-glucoside and alpha-isomaltoside. These oligosaccharides were not fermented to an acid by Streptococcus mutans, and they effectively inhibited water-insoluble glucan synthesis from sucrose by glucosyltransferase. In an in vitro utilization test with human intestinal bacteria, these oligosaccharides were predominantly utilized by Bifidobacteria.
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PMID:Synthesis by an alpha-glucosidase of glycosyl-trehaloses with an isomaltosyl residue. 914 29

The properties of the N-glycan processing glycosidases located in the endoplasmic reticulum of Saccharomyces cerevisiae are described. alpha-Glucosidase I encoded by CWH41 cleaves the terminal alpha1, 2-linked glucose and alpha-glucosidase II encoded by ROT2 removes the two alpha1,3-linked glucose residues from the Glc3Man9GlcNAc2 oligosaccharide precursor while the alpha1,2-mannosidase encoded by MNS1 removes one specific mannose to form a single isomer of Man8GlcNAc2. Although trimming by these glycosidases is not essential for the formation of N-glycan outer chains, recent studies on mutants lacking these enzymes indicate that alpha-glucosidases I and II play an indirect role in cell wall beta1,6-glucan formation and that the alpha1,2-mannosidase is involved in endoplasmic reticulum quality control. Detailed structure-function studies of recombinant yeast alpha1,2-mannosidase are described that serve as a model for other members of this enzyme family that has been conserved through eukaryotic evolution.
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PMID:Processing glycosidases of Saccharomyces cerevisiae. 987 80

Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
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PMID:Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat. 1038 96

The mechanism of nutrient-evoked insulin release is clearly complex. One part of that mechanism is postulated to be the activation of the glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. As nitric oxide (NO) has been found to be a potent inhibitor of glucose-stimulated insulin secretion, we have now investigated a possible influence of exogenous NO and inhibition of endogenous NO production on islet acid glucan-1,4-alpha-glucosidase activity in relation to insulin release stimulated by glucose and l-arginine. In isolated islets, NO derived from the intracellular NO donor hydroxylamine inhibited the activation of acid glucan-1, 4-alpha-glucosidase and its isoform acid alpha-glucosidase in parallel with inhibition of glucose-stimulated insulin release. In comparison, other lysosomal enzymes were largely unaffected. Similarly, the spontaneous NO donor sodium nitroprusside, as well as NO gas, when added to islet homogenates, suppressed the activities of these acid alpha-glucosidehydrolases and, to a lesser extent, the activities of other lysosomal enzymes. Finally, in the presence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester, insulin release from isolated islets stimulated by glucose or l-arginine was markedly potentiated in parallel with an accompanying increase in the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase. Other lysosomal enzymes and neutral alpha-glucosidase were not influenced. We propose that an important inhibitory effect of NO on the insulin secretory processes stimulated by glucose and l-arginine is exerted via inactivation of islet acid glucan-1,4-alpha-glucosidase, a putative key enzyme in nutrient-stimulated insulin release.
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PMID:Nitric oxide, islet acid glucan-1,4-alpha-glucosidase activity and nutrient-stimulated insulin secretion. 1081 Feb 93

We examined the relation between nutrient-stimulated insulin secretion and the islet lysosome acid glucan-1,4-alpha-glucosidase system in rats undergoing total parenteral nutrition (TPN). During TPN treatment, serum glucose was normal, but free fatty acids, triglycerides, and cholesterol were elevated. Islets from TPN-infused rats showed increased basal insulin release, a normal insulin response to cholinergic stimulation but a greatly impaired response when stimulated by glucose or alpha-ketoisocaproic acid. This impairment of glucose-stimulated insulin release was only slightly ameliorated by the carnitine palmitoyltransferase 1 inhibitor etomoxir. However, in parallel with the impaired insulin response to glucose, islets from TPN-infused animals displayed reduced activities of islet lysosomal enzymes including the acid glucan-1,4-alpha-glucosidase, a putative key enzyme in nutrient-stimulated insulin release. By comparison, the same lysosomal enzymes were increased in liver tissue. Furthermore, in intact control islets, the pseudotetrasaccharide acarbose, a selective inhibitor of acid alpha-glucosidehydrolases, dose dependently suppressed islet acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase activities in parallel with an inhibitory action on glucose-stimulated insulin secretion. By contrast, when incubated with intact TPN islets, acarbose had no effect on either enzyme activity or glucose-induced insulin release. Moreover, when acarbose was added directly to TPN islet homogenates, the dose-response effect on the catalytic activity of the acid alpha-glucosidehydrolases was shifted to the right compared with control homogenates. We suggest that a general dysfunction of the islet lysosomal/vacuolar system and reduced catalytic activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase may be important defects behind the impairment of the transduction mechanisms for nutrient-stimulated insulin release in islets from TPN-infused rats.
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PMID:TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release. 1140 35


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