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)

Because the pancreas undergoes involutional changes during total parenteral nutrition (TPN) and because pancreatico-biliary secretions are trophic to the intestine, we studied jejunal and ileal structure and function and exocrine pancreatic function before and after 6 weeks of TPN in two groups of beagle dogs, one of which had TPN alone, the other having TPN plus daily stimulation of pancreatico-biliary secretions with intravenous infusions of cholecystokinin (CCK) and secretin. The injections of 1 U each per kg of body weight per day of CCK and secretin completely prevented the proximal and distal small bowel mucosal hypoplasia which developed in the TPN alone group. They also resulted in significant increases in in vivo galactose absorption (64 mM) per unit length of jejunum and ileum. However, there was no significant change in mucosal alpha-glucosidase and catalase activity or in in vitro mucosal uptake of 1 mM [14C]leucine when expressed per unit weight of intestinal mucosa. The capacity of the pancreas to respond to CCK and secretin was unaffected by excluding food from the intestine with 6 weeks of TPN in terms of pH, volume, and peak secretion rates of bicarbonate and protein, but maximum amylase output (units per 15 min per kg of body weight) fell significantly (P less than 0.05) from a mean of 1022 +/- 155 to 874 +/- 426 in TPN alone group and to 472 +/- 79 in the TPN dogs given CCK and secretin. These results show that daily CCK and secretin is trophic to the intestine of dogs nourished by TPN but do not indicate whether this trophic effect is attributable to CCK alone, secretin alone, the combination of the two hormones, or to the resultant stimulation of pancreatico-biliary secretions.
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PMID:Cholecystokinin and secretin prevent the intestinal mucosal hypoplasia of total parenteral nutrition in the dog. 12 2

Digestive enzymatic activities (disaccharidases, alkaline phosphatase, peptide hydrolases) have been determined in the mucosa of 14 patients with chronic pancreatitis. All had an abnormal secretin-pancreozymin test. Four patients had insulin-dependent diabetes mellitus, four a pathological glucose tolerance test. Nine patients had steatorrhoea. Maltase, sucrase, and alkaline phosphatase activity was significantly elevated in patients with exocrine pancreatic insufficiency, whereas those of lactase, trehalase, and peptide hydrolase were normal. Patients with steatorrhoea had higher maltase and sucrase activity than those without steatorrhoea, whereas decreased glucose tolerance had no effect on brush border enzymatic activity. It is suggested thatdecreased exocrine rather than decreased endocrine pancreatic function is responsible for the increase in intestinal disaccharidase and alkaline phosphatase activity, possible by the influence of pacreatic enzymes on the turnover of brush border enzymes from the luminal side of the mucosal membranes or by direct hormonal stimulation though cholecystokinin.
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PMID:Influence of exocrine and endocrine pancreatic function on intestinal brush border enaymatic activities. 109 2

The effects of repeated oral administration of the synthetic trypsin inhibitor camostat on intestinal macromolecular transport and disaccharidase development were investigated in suckling rats. By daily treatment with camostat, bovine immunoglobulin (Ig) G transport in the intestine declined more rapidly in treated than in control rats. The absorption curve shifted to the left in treated rats 3 days before the controls. Morphological inspection of treated pups showed a decline in the number of epithelial cells that absorb bovine IgG and in their vesicle size from basal to upper regions of the villi. Maltase activity precociously increased with camostat treatment. Chronic subcutaneous injection of camostat did not cause any changes in IgG transport and maltase activity. The depression of IgG transport by oral treatment with camostat was not affected by the cholecystokinin (CCK) receptor antagonist L 364718 and was not inhibited by adrenalectomy. The absorptive responses of IgG and maltase activity were not affected by CCK-8 treatment. These data indicate that oral administration of camostat induces precocious maturation of the small intestine and that the effect is not mediated via endogenous CCK released by camostat.
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PMID:Precocious cessation of intestinal macromolecular transport by synthetic trypsin inhibitor in suckling rats. 144 38

This study investigates digestive and lysosomal enzyme secretion of azaserine-induced pancreatic acinar carcinomas in response to cholecystokinin in rats. After 15-20 months of treatment, 95% of the animals developed pancreatic acinar carcinomas encompassing more than 90% of the tissue. In anesthetized rats basal trypsin output was significantly elevated in the tumor group despite diminished fluid secretion. There was a linear correlation between tumor size and basal amylase and trypsin secretion. Intravenous infusion of cholecystokinin (25 IDU.kg-1.h-1) induced a significantly lower secretion of fluid per gram pancreas, as well as decreased amylase and trypsin output, in the tumor group compared with the control group. Plasma amylase and lipase levels were significantly elevated in the tumor group under both basal and stimulated conditions. The output of the lysosomal enzymes beta-D-glucuronidase and alpha-D-glucosidase was significantly increased in the tumor group under background secretin infusion. Additional cholecystokinin infusion caused a sharp increase in glucuronidase output in this group with only minimal increase in controls. Glucosidase output increased similarly in both groups. Amylase, lipase, and trypsin tumor tissue concentrations were markedly reduced by 85%, 90%, and 87%, respectively. It was concluded that the decreased secretory response of digestive enzymes may result from decreased synthesis, lowered storage capabilities, and/or a decreased/increased responsiveness to cholecystokinin. Increased glucuronidase secretion may reflect an augmented cell turnover of malignant tissue.
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PMID:Secretagogue response of azaserine-induced rat pancreatic acinar tumors in vivo. 171 May 88

Glucagon is structurally related to secretin but inhibits the effects of secretin and cholecystokinin (CCK) on pancreatic secretion in vivo. Because secretin is a weak stimulant of pancreatic growth and potentiates the trophic effects of CCK, we hypothesized that glucagon might inhibit CCK-induced pancreatic growth. Four groups of 10 rats were injected with saline, glucagon (30 micrograms/kg, equimolar to a known trophic dose of secretin), cerulein (0.67 microgram/kg), or glucagon plus cerulein every 8 h for 5 days. The pancreas was excised, weighed, and assayed for total content of DNA, protein, amylase, chymotrypsinogen, and lipase. In control and glucagon-alone groups, the small intestine was also removed, weighed, and assayed for DNA, protein, and disaccharidase content. Glucagon alone decreased pancreatic DNA and increased lipase content. Compared with cerulein-treated animals, animals treated with glucagon and cerulein showed significant decreases in pancreatic weight and content of protein, amylase, and chymotrypsinogen. Although glucagon had significant effects on intestinal protein, maltase, and sucrase contents in certain segments, there was no clear pattern of response. The data suggest that glucagon may be an inhibitory regulator of pancreatic growth, acting to block the effects of CCK on pancreatic hypertrophy.
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PMID:Glucagon inhibition of cerulein-induced hypertrophy of the exocrine pancreas. 336 38

The effect of pentagastrin, secretin and cholecystokinin on biochemical parameters of mucosal growth and differentiation was studied in organ cultured rabbit jejunum and ileum. Pentagastrin at 0.05-5.0 microgram/ml did not affect DNA content of the biopsy, but led to a significant decrease of sucrase and alkaline phosphatase activity in the ileum. Secretin prompted a significant decrease of DNA and protein in the ileum at a level of 10(-7) and 10(-5) M, but had no effect in the jejunum. Of the brush border enzymes, sucrase and alkaline phosphatase were suppressed in both parts of the intestine both with respect to specific activity and total biopsy content. Cholecystokinin, like pentagastrin, did not influence DNA or protein content, but reduced sucrase, maltase and alkaline phosphatase activity. HMG-CoA reductase, the key enzyme of cholesterol synthesis, was not significantly affected by any of the three hormones tested. When brush border enzymes or DNA from desquamated cells were measured in the post-culture medium, no consistent effect of any gastrointestinal hormone was apparent. The present study demonstrates a direct "antitrophic" effect of secretin in cultured mucosa. Pentagastrin and cholecystokinin did not influence mucosal DNA content in vitro but apparently inhibited villus cell differentiation.
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PMID:Effect of pentagastrin, secretin and cholecystokinin on growth and differentiation in organ cultured rabbit small intestine. 372 4

The results presented show striking differences in the response of the exocrine pancreas to fasting in suckling versus adult rats. In adult rats, fasting led to an increase in lipase to amylase ratio with a particularly sharp decrease in amylase concentrations, a generalized decrease in total protein, amylase, trypsinogen and lipase contents, and a decrease in responsiveness of the pancreatic acini to optimal and supraoptimal concentrations of secretagogues in vitro. In 15 day old pups, however, fasting led to an increase in total amylase, trypsin and lipase and a maintenance of the total protein content in their pancreases. Further, no decrease in responsiveness of their pancreatic acini to secretagogue stimulation is observed at the concentrations studied. The difference in the behavior of the exocrine pancreas during fasting can be partly explained by the changing pattern of their responses to hormonal stimulation, particularly that of corticosterone and cholecystokinin during various stages of development. Fasting led to an increase in corticosterone and presumable decrease in cholecystokinin. The pancreas of the suckling rat is very sensitive to the induction effect of corticosterone while that of the adult rats is relatively insensitive. Conversely, the pancreas of the adult rats is sensitive to the trophic effect of cholecystokinin while that of the suckling rat has the opposite reaction. The combination of these and other factors then resulted in an entirely different profile of the responses of the exocrine pancreas to fasting. Recent studies in our laboratory, and that of others, showed that an analogous situation also existed in the small intestine. Fasting of adult rats led to a general decrease in small intestinal enzymes including sucrase and maltase (29) but in suckling rats led to (30,31) increases of sucrase and maltase. Corticosterone again has been shown to be involved (30,31). Further, the small intestinal sucrase of the suckling rats responded to corticosterone by an increase in its level but the same hormone did not seem to control the sucrase concentrations in the small intestine of adult rats (32,33). Thus, both the small intestine and the pancreas responds very differently to fasting presumably mediated through a varying pattern of responses to selective hormonal stimulation, eg in this case, corticosterone. These results strongly suggest the importance of the interaction between environmental influences (fasting in this case) and the stage of development in determining the outcome of ontogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Response of the pancreas to fasting: adult versus neonates. 620 75

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

The aim of this study was to determine the effects of a model of intestinal extrinsic denervation on mucosal structure and function. Six dogs underwent in situ neural isolation of the jejunoileum (Group 2); six other dogs served as operated controls (Group 1), and five nonoperated dogs were naive controls (Group 3). Thirty-centimeter segments of proximal jejunum and distal ileum were excised before (time zero) and at 2 weeks and 8 weeks postoperatively in Groups 1 and 2, while similar regions were removed at time zero in Group 3. Tissues were analyzed for morphology with quantitative morphometry, mucosal disaccharidase activities (sucrase, maltase, and lactase), and tissue content of selected regulatory peptides in transmural, mucosa/submucosa, and muscularis regions. In situ neural isolation had no significant or consistent effects on morphology/morphometry or on mucosal disaccharidase activities. Tissue content of neuropeptide Y decreased markedly (P < 0.002) in all layers of the jejunal and ileal walls, but tissue content of vasoactive inhibitory polypeptide, substance P, cholecystokinin, neurotensin, met-enkephalin, neurokinin A, somatostatin, and calcitonin gene-related peptide demonstrated only minor changes. The physiologic effects of intestinal transplantation (extrinsic denervation and disruption of intrinsic, enteric neural continuity, and lymphatic drainage) have little effect on morphology, mucosal disaccharidase activity, and tissue content of most regulatory peptides. How these minor alterations might affect enteric function, however, needs to be investigated.
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PMID:Neural isolation of the jejunoileum. Effect on tissue morphometry, mucosal disaccharidase activity, and tissue peptide content. 865 18


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