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)

1. The role of endogenous CCK in the development of digestive enzyme activities in small intestine and pancreas was investigated in suckling rats. Synthetic protease inhibitor (camostat 100 micrograms/g bwt) was orally administered twice daily for 5 days from 11 days of age. 2. Pancreatic hypertrophy and hyperplasia, and alteration of pancreatic enzyme composition, especially decreases in amylase activity and increases in trypsin and chymotrypsin activities were produced by camostat treatment. These changes were completely suppressed by simultaneous administration of the potent CCK receptor antagonist L-364,718 (1 microgram/g bwt). 3. With camostat treatment, intestinal lactase activity decreased to 41%, while maltase and sucrase activities increased 3 and 2.5 times respectively. These changes in enzyme activities were not affected by the application of L-364,718. 4. The mucosal disaccharidase and pancreatic enzyme activities could not be modified by chronic subcutaneous injection of camostat. The precocious induction of maltase and sucrase activities by camostat treatment was also observed in the adrenalectomized pups. 5. These results indicate that pancreatic growth accompanied by alteration of digestive enzyme composition in the suckling rats is regulated by endogenous CCK, but the precocious induction of disaccharidase activities is not mediated by endogenous CCK released by camostat treatment.
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PMID:Precocious alteration of digestive enzyme activities in small intestine and pancreas by chronic oral administration of protease inhibitor in suckling rats. 168 62

This report deals with the effect of feeding inhibitors of pancreatic and brush border enzymes on pancreatic growth and enzyme composition and secretion. Raw soybean flour containing trypsin inhibitors caused pronounced growth of the pancreas which was accompanied by increased enzyme content and increased CCK and gastrin concentration in the plasma. Feeding of an amylase inhibitor to a starch-rich diet induced a marked fall in amylase content and secretion without changing growth parameters of the pancreas, indicating that not starch but glucose is the trigger for the maintenance of amylase content and secretion of the pancreas. The addition of an alpha-glucosidase inhibitor (acarbose) to a sucrose- or maltose-rich semisynthetic diet did not cause significant alteration in pancreatic growth or enzyme composition or secretion. In man pancreatic function was also unaltered by 8 weeks' intake of 3 X 200 mg acarbose.
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PMID:Adaptation of the pancreas during treatment with enzyme inhibitors in rats and man. 240 82

Intestinal adaptation has been studied in rats with pancreatic atrophy induced by feeding a copper-deficient diet and penicillamine and in rats with carbohydrate maldigestion induced by feeding of an alpha-glucosidase inhibitor (acarbose). Pancreatic atrophy led to a significant increase of weight, protein, and DNA content as well as specific activities and total amounts of the enzymes sucrase and maltase in the distal but not in the proximal part of the small intestine. Plasma levels of CCK and GIP were significantly higher in rats with pancreatic atrophy, whereas plasma levels of gastrin and insulin were lower. Tissue concentrations of gastrin in the antrum and GIP in duodenum and jejunum were unchanged. Duodenal CCK and jejunal substance P, somatostatin, and VIP and ileal substance P and somatostatin were significantly decreased in rats with acinar atrophy. Glucosidase inhibition by acarbose feeding led to weight increase of the small intestine and cecum. This was more marked when acarbose was fed together with a fiber-free diet. Under these conditions the protein and DNA content also increased significantly in both gut segments and maltase and sucrase content predominantly in the distal part. Insulin plasma concentration decreased significantly in the acarbose-fed groups, whereas GIP, gastrin, and CCK plasma concentrations remained unchanged. After fiber-rich diet tissue concentrations of gastrin in the antrum and insulin in the pancreas were significantly higher and GIP concentrations in the duodenum and jejunum significantly lower than after fiber-free diet. Acarbose increased the pancreatic insulin concentration only in the fiber-free group and did not influence gastrin and GIP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptation of the small intestine to induced maldigestion in rats. Experimental pancreatic atrophy and acarbose feeding. 389 54

The possibility that pancreatic secretory abnormalities might precede the appearance of pancreatic neoplasms and thus provide clues to early detection of this malignancy has been investigated in an animal model. Syrian golden hamsters were treated with bis-(2-oxopropyl)-N-nitrosamine on two successive weeks (2 mg/100 g body weight/week). Pancreatic secretions from treated and untreated control animals were studied at approximately monthly intervals. The animals were anesthetized, their pancreatic ducts cannulated, and basal pancreatic juice collected for 30 min. Pancreatic secretion was then stimulated by sequential intravenous injection of secretin (50 ng/100 g) and C-terminal octapeptide of cholecystokinin (4 ng/100 g) 1 hr later. Four consecutive 15-min collections of fluid were made following secretin stimulation and four additional collections after CCK administration. Each collection was examined for volume, total protein, trypsin, chymotrypsin, elastase, arylsulfatase, beta-D-glucuronidase, alpha-D-glucosidase, and leucine naphthylamidase. In addition two trypsinogen variants present in pancreatic secretions were determined. The pancreas and other organs were removed and examined histologically at the end of each experiment. Cytological atypia appeared 3 months, ductal hyperplasia 4 months, and pancreatic neoplasms 6 months after the last injection of carcinogen. Striking decreases in flow rate and output of trypsin and chymotrypsin were observed several months prior to the appearance of histologically recognizable pancreatic tumors. By contrast, output of beta-D-glucuronidase and alpha-D-glucosidase in pancreatic juice increased markedly in the last 2 months preceding the emergence of neoplasms. The diagnostic significance of these premalignant abnormalities is illustrated most dramatically in the form of ratios of lysosomal to digestive enzymes, such as beta-D-glucuronidase-trypsin or alpha-D-glucosidase-chymotrypsin. Highly significant increases in these ratios were observed consistently, not only in hamsters with pancreatic neoplasms, but also in animals with preneoplastic lesions (ductular hyperplasia) which preceded malignancies by about 2 months.
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PMID:Pancreatic secretory abnormalities precede appearance of tumors of the pancreas in hamsters treated with bis-(2-oxopropyl)-N-nitrosamine. 630 6

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

We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.
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PMID:Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release. 1151 88