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:3.2.1.26 (invertase)
4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal sucrose hydrolysis and absorption of monosaccharide products was studied in vivo utilizing the segmental perfusion technique in diabetic and control rats. The proximal jejunum was perfused with 20 mM sucrose, 140 mM NaCl and 0.5% PEG with 14C-PEG, as the nonabsorbable marker. Rates of sucrose hydrolysis and adsorption of monosaccharide products (fructose, and glucose) were determined. There were no statistically significant differences between the diabetic and control rats. This indicates that the previously reported increase in sucrase activity in diabetes does not correlate with enhanced rates of sucrose hydrolysis. Several possibilities for the interpretation of these results are discussed.
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PMID:Intestinal digestion and absorption of sucrose in experimental diabetes. 102 Jun 13

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

Increased sucrase-isomaltase (SI) expression is a prominent feature of adaptive changes observed in the small intestine of streptozocin-treated chronically diabetic (CD) rats. In this study, we examine the cellular and molecular basis of increased SI expression in CD rats by determining SI specific activities and mRNA abundance in sequentially isolated enterocytes along the villus-to-crypt axis of proximal jejunum and distal ileum. In all regions, two- to fourfold increases in sucrase activity in diabetic rat enterocytes were paralleled by increases in SI mRNA. However, analogous to nondiabetic rat intestine, no differences in SI mRNA abundance were observed between corresponding enterocyte fractions from ileum and jejunum of diabetic rat intestine. By nuclear run-on assays, differences in rates of SI gene transcription were not observed in diabetic and nondiabetic intestinal tissues. We conclude that diabetes induces increased total and specific activities and mRNA abundance of intestinal SI, largely through the stabilization of SI mRNA. Furthermore, analogous to nondiabetic small intestine, differences in proximal-to-distal SI expression appear to be determined at the translational or posttranslational level.
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PMID:Altered regulation of regional sucrase-isomaltase expression in diabetic rat intestine. 161 47

In ad libitum-fed diabetic rats, sucrase specific activities in jejunum and ileum were significantly increased two- to threefold compared to controls, a response unaltered by pair-feeding. Gradients of sucrase activities along the ileal villus-to-crypt axis were readily measured in crypt regions in diabetic, but not in nondiabetic, rats. Changes in sucrase activities were commensurate with increases in sucrase immunoreactivity and not a result of altered functional activity. Insulin treatment reversed these effects, although insulin-deficiency, studied in food-deprived, nondiabetic rats, did not affect sucrase expression. We conclude that chronic diabetes significantly stimulates sucrase expression along the proximal-to-distal and villus-to-crypt axes of rat small intestine. In ileum, these changes suggest marked alterations in phenotypic development of enterocytes along the villus-to-crypt axis. Alterations in sucrase expression do not appear to correlate with insulin states and are not a consequence of altered functional activity.
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PMID:Regional alterations in intestinal sucrase expression in streptozocin-treated chronically diabetic rats. 161 56

AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKA(y), were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22 mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21 mg/kg. Four-week-old female KKA(y) mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKA(y) mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). 162 84

Variations in the dietary fatty acid composition and cholesterol content are associated with alterations in the intestinal uptake of hexoses and lipids in control and diabetic rats. Changes in the composition of the brush membrane (BBM) lipids may provide a possible mechanism for the observed alterations in transport properties. Accordingly, control and streptozotocin diabetic animals were fed one of four isocaloric semisynthetic diets for two weeks: beef tallow with low cholesterol, beef tallow with high cholesterol, fish oil with low cholesterol or fish oil with high cholesterol. BBM were prepared and assessed for marker enzyme activity and lipid composition. Fish oil feeding was associated with a reduction in total phospholipid content in control and diabetic jejunal and ileal BBM; this fall in total phospholipids was due to a reduction in BBM sphingomyelin. Cholesterol supplementation increased control jejunal BBM sucrase activity in animals fed beef tallow but reduced sucrase activity in animals fed fish oil. In fish oil fed diabetic animals, jejunal and ileal BBM alkaline phosphatase activity was increased with cholesterol supplementation. The elevation in BBM total phospholipids (phosphatidylethanolamine) associated with diabetes in beef tallow fed animals was not observed in the jejunal BBM of animals fed fish oil or in the ileal BBM of animals fed fish oil with high cholesterol. Thus, (a) feeding an omega-3 polyunsaturated fatty acid diet (fish oil) reduced total phospholipid content in BBM of control and diabetic animals, primarily due to a reduction in sphingomyelin; and (b) feeding an omega-3 polyunsaturated fatty acid diet or dietary cholesterol supplementation alter the activity of BBM enzymes. These results suggest that variations in dietary fat composition and the associated changes in BBM composition and enzyme activity contribute to altered intestinal function in diabetes.
Diabetes Res 1991 Mar
PMID:Isocaloric modification of dietary lipids influences intestinal brush border membrane composition in diabetic rats. 180 79

BioBreed (BB) Wistar rats develop diabetes mellitus, which closely resembles the human disease, in 50% of progeny. Intestinal sucrase-alpha-dextrinase, a glycoprotein hydrolase of the enterocyte's brush border consisting of 140-kDa alpha-dextrinase and 125-kDa sucrase subunits, is essential for surface digestion of carbohydrate nutrients. Although its catalytic characteristics were found to be maintained in the diabetic state, the structure of the subunits, as compared with normal Wistar rats, was altered in the BB rat within 2 days of the onset of diabetes. Its capacity to react in a solid-phase immunoassay was reduced by 50%; when examined by 6% acrylamide electrophoresis, the sucrase subunit was increased in mass by 5 kDa and, in some BB rats, the dextrinase subunit was reduced by 5 kDa. Intact rats labeled intraintestinally with [35S]methionine displayed the alteration within 6 h of synthesis, indicating that nonenzymatic glycosylation could not account for the structural change. This mass change was not seen in streptozotocin-induced diabetes and was independent of the plasma glucose concentration or the degree of acidosis. Deglycosylation with peptide N-glycosidase indicated that the N-linked chains of the normal dextrinase subunit (11 kDa) have twice the mass of those in the BB rat (6 kDa) and that the sucrase subunit may have an increased mass of O-linked chains. Overall, these experiments point to changes in glycosylation as a mechanism of structural alteration in congenital diabetes. Despite persistence of the insulin-dependent diabetes, the subunit pattern eventually became indistinguishable from normal, but at differential rates (21 days and 35 days, respectively, for sucrase and dextrinase subunits).
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PMID:Sucrase-alpha-dextrinase in diabetic BioBreed rats: reversible alteration of subunit structure. 199 46

Inhibition of intestinal alpha-glucohydrolase activity is one approach for reducing the glycemic response from dietary carbohydrate and may prove useful for the treatment of diabetes mellitus. In this article, we describe the pharmacological properties of a time-dependent intestinal alpha-glucohydrolase inhibitor, MDL 73945. When preincubated 2 h with a rat intestinal mucosa preparation before substrate addition, MDL 73945 was a potent inhibitor of sucrase, maltase, glucoamylase, and isomaltase activities (MDL 73945 concentrations required to cause a 50% decrease in enzyme activity, 2 x 10(-7), 1 x 10(-6), 5 x 10(-6), and 8 x 10(-6) M, respectively); without preincubation, it was 10- to 500-fold less potent. In rats, a single oral dose of MDL 73945 administered simultaneously with 2 g/kg body wt sucrose resulted in a dose-dependent reduction in the area under the 0- to 3-h glycemic response curve, which was significant at 1 (45% reduction) and 3 (65% reduction) mg/kg. When administered 1 h before sucrose, the compound was more potent, with 0.3 mg/kg MDL 73945 significantly reducing the glycemic response to sucrose by 62%. A reduction in the glycemic response to sucrose was accompanied by reduced insulin secretion. MDL 73945 was slightly less effective against a starch load, with 3 and 10 mg/kg MDL 73945 administered 0.5 h before starch reducing the glycemic response by 39 and 52%, respectively. MDL 73945 was more effective against a sucrose load in streptozocin-administered rats than in control rats and was as effective after 16 daily doses as after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jul
PMID:New potent alpha-glucohydrolase inhibitor MDL 73945 with long duration of action in rats. 206 Jul 19

Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolase inhibitors in rats. 7-O-alpha-D-Glucopyranosyl-CS (7 alpha-glc-CS) and 8 alpha-glc-CS were potent sucrase inhibitors with IC50s of 40 and 30 nM, respectively. Their sucrase inhibition was poorly reversible. They were much weaker liver lysosomal alpha-glucosidase inhibitors with IC50s of 40,000 nM. 1 alpha-glc-CS and 8 beta-glc-CS were both weaker and less selective sucrase inhibitors. In vivo, 7 alpha-glc-CS and 8 alpha-glc-CS effectively reduced the glycemic response to an oral 2 g/kg sucrose load at doses less than or equal to 1 mg/kg. 8 alpha-glc-CS was effective when administered up to 4 hr before sucrose. The known glucohydrolase inhibitors 1-deoxynojirimycin and N-hydroxyethyl-1-deoxy-nojirimycin were also potent sucrase inhibitors (IC50s = 200 and 400 nM, respectively) but their sucrase inhibition was readily reversible in vitro and their in vivo duration of action was much shorter than for the CS-glcs. Among the glucohydrolase inhibitors tested, the prolonged in vivo duration of action could be predicted by poor reversibility from sucrase. These CS-glcs provide a new generation of sucrase inhibitors which may be useful in the treatment of diabetes mellitus.
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PMID:Castanospermine-glucosides are potent, selective, long-acting sucrase inhibitors. 267 17

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.
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PMID:Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats. 286 16


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