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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimentally induced diabetes enhances the specific activity of several microvillus membrane proteins in the rat small intestine. The increase in the specific activity of sucrase-isomaltase has been shown by others to be due to an increase in enzyme protein, raising the possibility that diabetes induces a generalized increase in microvillus membrane proteins. Since intramembrane particles (IMPs) seen on freeze-fracture replicas of microvillus membranes are thought to represent integral membrane proteins, we compared microvillus IMP densities in diabetic rats with those in control rats. In addition, mucosal sucrase, maltase, and alkaline phosphatase specific activities were measured in all animals. Diabetic rats had significantly increased sucrase and maltase but not alkaline phosphatase specific activities compared with control rats. The density of microvillus IMPs on both the protoplasmic and extracellular fracture faces of undifferentiated crypt cells and villus absorptive cells was not increased in experimental diabetes. These data indicate that diabetes does not result in a generalized increase in microvillus membrane proteins. Thus the enhanced activity of microvillus membrane proteins in diabetes appears to be highly selective.
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PMID:Structural features of the rat small intestinal microvillus membrane in acute experimental diabetes. 704 26

The effect of food restriction on the intestinal weight and membrane digestive enzyme activities was observed in rats with diabetes induced by streptozotocin. The specific activities of disaccharidases of food non-restricted diabetic rats were not changed, but total activities were significantly increased due to the increase of intestinal mucosal weight. Restriction of food intake did not increase intestinal mucosal weight, but significantly increased the specific and total activities of disaccharidases in parallel with the increase of sucrase-isomaltase content. On the other hand, experimental diabetes did not influence the activity of alkaline phosphatase and leucine aminopeptidase except for specific and total activities of alkaline phosphatase in food non-restricted rats.
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PMID:Effect of food restriction on intestinal disaccharidases in streptozotocin-induced diabetes of rat. 724 Dec 40

An abnormally high level of the sucrase-isomaltase (SI) complex in the small intestine of rats with streptozotocin-induced insulin-dependent diabetes mellitus (IDDM) was normalized in 11 h by the administration of insulin, in addition to normalization of the blood glucose level. Phlorizin, an inhibitor of renal glucose reabsorption, also caused normalization of the blood glucose level in the IDDM rats; however, the level of the SI complex was barely changed. When mucosa explants were cultured in a medium, the SI complex synthesized during the cultivation was accumulated as its precursor protein without maturation, owing to the absence of pancreatic proteases, and the amount of the precursor protein that accumulated in the explants was decreased by the addition of insulin into the medium. Further, the mRNA level of the SI complex in the explants incubated with insulin was obviously lower than that in the absence of insulin. These results indicate that insulin has a suppressive effect on the synthesis of the SI complex, presumably by decreasing the transcriptional level of the gene encoding the complex, in small-intestinal epithelial cells. Thus the synthesis of the SI complex might exceed normal levels in the epithelial cells as a direct result of the depletion of insulin under IDDM conditions.
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PMID:Suppressive effect of insulin on the synthesis of sucrase-isomaltase complex in small intestinal epithelial cells, and abnormal increase in the complex under diabetic conditions. 944 87

The drugs used to treat diabetes mellitus are diverse and involve several classes. However, these drugs can be roughly separated into hypoglycaemic agents, such as insulin and the sulphonylureas, and antihyperglycaemic agents, such as the biguanides, the alpha-glucosidase inhibitors and troglitazone. Reports of insulin overdose are rare. The major effects of insulin overdose are secondary to the insult to the CNS produced by hypoglycaemia. The mainstay of insulin overdose management is glucose replacement therapy. Sulphonylureas are the most commonly used oral antihyperglycaemic agents in the management of type 2 (non-insulin-dependent; NIDDM) diabetes mellitus. Sulphonylureas primarily cause serum glucose reduction by stimulating the release of preformed insulin from the pancreatic islets. The mainstay of sulphonylurea overdose management is glucose replacement therapy, and in severe cases, reduction of insulin release. In the large majority of patients intravenous glucose supplementation will be sufficient to maintain euglycaemia. Repaglinide, a meglitinide analogue, is a new nonsulphonylurea oral hypoglycaemic agent. In overdose, this drug may produce prolonged hypoglycaemia similar to the sulphonylureas. The primary problem with biguanide overdose is the potential for lactic acidosis. The management of biguanide overdose is largely supportive and directed at correcting the metabolic acidosis along with associated complications. The alpha-glucosidase inhibitors, acarbose, voglibose and miglitol competitively and reversibly inhibit the alpha-glucosidase enzymes (glucoamylase, sucrase, maltase and isomaltase) in the brush border in the small intestine, which delays the hydrolysis of complex carbohydrates. They appear unlikely to produce hypoglycaemia in overdose, but abdominal discomfort and diarrhoea may occur. Troglitazone is the first thiazolidinedione antidiabetic drug available. There are no data on overdose, probably because of its very recent introduction. Overdoses with antidiabetic drugs produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare when treatment is initiated early. The management of the hypoglycaemic drugs (insulin and sulphonylureas) is based primarily on restoring and maintaining euglycaemia via intravenous dextrose supplementation. In the case of the sulphonylureas, reduction of insulin secretion via pharmacological intervention may also be necessary. With biguanides the main risk appears to be cardiovascular collapse secondary to profound acidosis. The management focus is on restoring acid-base balance with hyperventilation and the use of insulin to shift the utilisation of glucose from the nonoxidative pathway to the oxidative pathway. Use of haemodialysis has shown equivocal results but may be valuable in metformin overdose.
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PMID:Management of antidiabetic medications in overdose. 982 53

To clarify the relationship between diabetes mellitus and carbohydrate digestion, the activities of sucrase and isomaltase, which form a complex enzyme (SI complex) on the brush border membranes, were compared in the progression of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resistance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic controls. Until 40 weeks of age, OLETF rats were obese and had a high plasma glucose level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM became very severe with advancing insulin resistance in OLETF rats. In OLETF rats, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrease in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF rats; however, at 40 and 48 weeks of age, the plasma insulin level in the non-fasting state in OLETF rats was not significantly different from that in LETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level.
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PMID:Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance. 987 8

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.
Diabetes Res Clin Pract 2003 Feb
PMID:Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats. 1256 Jan 60

The small intestine plays an important role in the digestion and absorption of many nutrients. To investigate the contribution of carbohydrate digestion to diabetes mellitus, we examined the morphological changes of the small intestine, and the expression of sucrase-isomaltase, which is one of the intestinal disaccharidases, in diabetic model rat, that is the streptozotocin-induced (STZ) diabetic rat (insulin-deficient model), and the Otsuka Long-Evans Tokushima Fatty (OLETF) rats and the Goto-Kakizaki (GK) rats (type 2 diabetic models). Intestinal hyperplasia was observed in STZ, OLETF, and GK rats. Moreover, in the small intestine of each diabetic strain, the proliferating cell nuclear antigen (PCNA)-labeling index, which is a marker of proliferation, was higher than in the respective control. Cdx1 and Cdx2, known to be transcriptional factors related to intestinal proliferation and differentiation, were more highly expressed in STZ, OLETF and GK rats than in the respective controls. These findings indicate that small intestinal hyperplasia, and thereby the resultant increase of total activity of disaccharidases such as sucrase and isomaltase in the entire small intestine, might be one of the reasons for postprandial hyperglycemia in diabetes mellitus.
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PMID:Morphological changes and increased sucrase and isomaltase activity in small intestines of insulin-deficient and type 2 diabetic rats. 1294 Apr 55

Mutations in transcription factors hepatocyte nuclear factors (HNF)-1alpha and HNF-1beta cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. HNF-1alpha and HNF-1beta mutations are well studied in some tissues, but the mechanism by which HNF-1alpha and HNF-1beta mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. We studied the effects of 13 HNF-1alpha mutants and 2 HNF-1beta mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. Transactivation activity of 11 HNF-1alpha and 2 HNF-1beta mutants was significantly lower than that of wild (wt)-HNF-1alpha and wt-HNF-1beta. Furthermore, in co-expression studies with mutant (mu)-HNF-1alpha/ wt-HNF-1beta and wt-HNF-1alpha/mu-HNF-1beta, the combination of mu-HNF-1alpha (P379fsdelCT and T539fsdelC)/wt-HNF-1beta impaired SI transcription, but the others were not remarkably different from wt-HNF-1alpha/wt-HNF-1beta. Although wt-HNF-1beta inhibited the transactivation activity of wt-HNF-1alpha on SI transcription, the inhibitory effect was reduced by 2 HNF-1beta mutants. These results suggest that SI transcription might tend to be unchanged or lower in MODY3, while occurring more in MODY5.
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PMID:Effect of mutations in HNF-1alpha and HNF-1beta on the transcriptional regulation of human sucrase-isomaltase in Caco-2 cells. 1552 34

The inhibitory effect on human and rat intestinal disaccharidase by the extractive from the leaves of Morus alba (ELM) containing 0.24 % 1-deoxynojirimycin equivalent and its inhibitory activities were investigated by the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution, the sucrase activity of four human samples was inhibited by 96 % and that of maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase activities varied from sample to sample because the samples were obtained from different resected regions after surgery. However, the ratio of the inhibitory effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar among the four samples, and also that of resembled rat intestinal disaccharides. The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase and isomaltase was 2.1 x 10(-4), 2.5 x 10(-4) and 4.5 x 10(-4) mm, respectively, and these inhibitory activities were shown, using rat brush border membrane vesicles, to be competitive. These results demonstrate that digestion is inhibited when an appropriate amount of ELM is orally ingested with sucrose or polysaccharide in man. When ELM was orally administered in a sucrose solution to fasted rats, the elevation in blood glucose was significantly suppressed, depending on the concentration of ELM given. These results suggest that ELM could be used as an ingredient in health foods and in foods that help to prevent diabetes.
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PMID:Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity. 1661 83

Chebulagic acid, isolated form Terminalia chebula Retz, proved to be a reversible and non-competitive inhibitor of maltase with a K(i) value of 6.6 muM. The inhibitory influence of chebulagic acid on the maltase-glucoamylase complex was more potent than on the sucrase-isomaltase complex. The magnitude of alpha-glucosidase inhibition by chebulagic acid was greatly affected by its origin. These results show a use for chebulagic acid in managing type-2 diabetes.
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PMID:Chebulagic acid is a potent alpha-glucosidase inhibitor. 1825 69


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