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)

The hypoglycemic effect and the alpha-glucosidase activity inhibition of acarbose (AC:alpha-glucosidase inhibitor) were investigated in normal and KK-Ay mice, an animal model of noninsulin-dependent diabetes mellitus (NIDDM). AC improved hyperglycemia after an oral administration of maltose or sucrose, dose dependently in normal mice (1, 10, and 50mg/kg body weight) and in KK-Ay mice (50mg/kg). Furthermore, AC (50mg/kg) significantly inhibited maltase and sucrase activities in the small intestines of normal and KK-Ay mice (inhibitory efficacy: sucrase > maltase). The enzymatic inhibition in KK-Ay mice is stronger than in normal mice. However, AC (50 mg/kg) did not suppress the blood glucose in oral lactose tolerance and did not inhibit the lactase activity in either normal or KK-Ay mice. These findings indicate that the AC effect on the inhibition of alpha-glucosidase activity is selective for sucrase and maltase in normal and NIDDM mice.
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PMID:Effect of acarbose (alpha-glucosidase inhibitor) on disaccharase activity in small intestine in KK-Ay and ddY mice. 974 58

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

Noninsulin-dependent diabetes mellitus (NIDDM) is an increasingly common disease, which brings a number of life-threatening complications. In rats with experimentally induced diabetes, there is an increase in the capacity of the intestine to absorb monosaccharides. We have examined the activity and the expression of monosaccharide transporters in the intestine of patients suffering from NIDDM. Na(+)-dependent D-glucose transport was 3.3-fold higher in brush-border membrane (BBM) vesicles isolated from duodenal biopsies of NIDDM patients compared with healthy controls. Western analysis indicated that SGLT1 and GLUT5 protein levels were also 4.3- and 4.1-fold higher in diabetic patients. This was associated with threefold increases in SGLT1 and GLUT5 mRNA measured by Northern blotting. GLUT2 mRNA levels were also increased threefold in the intestine of diabetic patients. Analysis of other BBM proteins indicated that the activity and abundance of sucrase and lactase were increased by 1.5- to 2-fold and the level of the structural proteins villin and beta-actin was enhanced 2-fold in diabetic patients compared with controls. The increase in the capacity of the intestine to absorb monosaccharides in human NIDDM is due to a combination of intestinal structural change with a specific increase in the expression of the monosaccharide transporters SGLT1, GLUT5, and GLUT2.
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PMID:Expression of monosaccharide transporters in intestine of diabetic humans. 1180 45

Chromatographic separation of the pod extract of Angylocalyx pynaertii resulted in the isolation of 13 sugar-mimic alkaloids (1-13). The structures of the new alkaloids were elucidated by spectroscopic methods as the 6-O-beta-D-glucoside (10) and N-hydroxyethyl derivative (11) of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (1), 1,6-dideoxynojirimycin (12), and 1,3,4-trideoxynojirimycin (13). 2,5-Imino-1,2,5-trideoxy-L-glucitol (7), 2,5-dideoxy-2,5-imino-D-fucitol (8), and beta-homofuconojirimycin (9), isolated from the pods as well as the bark, were very specific inhibitors of alpha-L-fucosidase with no significant inhibitory activity toward other glycosidases. In this work, 1,4-dideoxy-1,4-imino-D-ribitol (6) was found to be a better inhibitor of lysosomal beta-mannosidase than 2,5-imino-1,2,5-trideoxy-D-mannitol (2). N-Hydroxyethyl-1-deoxynojirimycin (miglitol), which is commercially available for the treatment of diabetes, retained its inhibitory potential toward rat intestinal maltase and sucrase, whereas 11 and the synthetic N-hydroxyethyl derivative of 2,5-dideoxy-2,5-imino-D-mannitol markedly lowered or abolished their inhibition toward all enzymes tested.
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PMID:New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii. 1185 56

Summary. Many studies have shown that experimental type 1 diabetes causes morphological, functional, and metabolic alterations in the small intestine. The more frequent form of the disease, type 2 diabetes, however, has been less studied. Here the influence of diabetes on the functionality of the small intestine was studied in an experimental diabetes model, with a certain degree of residual insulin secretion, specifically in the n0-STZ model. - The diabetic rats in this model were found to have glycaemia levels higher than in the controls (8.82 +/- 0.27 and 6.18 +/- 0.18 mmol/L; p < 0.01), while their plasma insulin levels were lower than in the control rats (2.65 +/- 0.32 and 3.60 +/- 0.25 ng/ml; p < 0.05). Although there were no significant variations in body weight between the two groups, both the weight and the length of the intestine were significantly greater (p < 0.05) in the diabetic rats than in the controls. The sucrase and maltase activities were greater (p < 0.01) in the proximal intestine of the diabetic rats (94 +/- 8 and 234 +/- 12 mU/mg protein, respectively) than in the control rats (50 +/- 2 and 149 +/- 20 mU/mg protein, respectively). The 6-phosphofructo-1-kinase activity (mU/mg proteins) was less (p < 0.05) in the proximal and distal intestine of the diabetic rats (160 +/- 40 and 80 +/- 20, respectively) than in the controls (280 +/- 30 and 230 +/- 30, respectively). No significant differences were observed in the lactate dehydrogenase or active and total pyruvate dehydrogenase measured in the distal and proximal intestine of control and diabetic rats. In conclusion, our results show that experimental diabetes (n0-STZ model) similar to human type 2 diabetes produces certain morphological and enzymatic alterations which affect the digestion and absorption of carbohydrates and the intestinal metabolism of glucose. These alterations may contribute to producing the post-prandial hyperglycaemia which characterizes diabetes.
Exp Clin Endocrinol Diabetes 2002 May
PMID:Morphological and enzymatic changes of the small intestine in an n0-STZ diabetes rat model. 1201 71

To elucidate the effect of feeding of butyric acid on disaccharidase activities, the specific activities of the disaccharidases were measured in the intestinal mucosa and kidney cortex of control and diabetic rats. Diabetes was induced in rats using streptozotocin. Rats were fed with basal diet containing wheat bran (5%) as a source of insoluble dietary fiber and guar gum (2.5%) as a source of soluble dietary fiber. The experimental group received butyric acid at 250, 500 and 750 mg/kg body weight/day. Increased activities of intestinal maltase, sucrase and lactase in diabetic rats were significantly reduced in fiber-fed diabetic group. Supplementation of butyric acid at 500 mg/kg body weight/day showed a further decrease in their activities. The activity of disaccharidases in renal tissue was decreased in diabetic rats and was significantly improved in fiber-fed diabetic group. Butyric acid feeding at 500 mg/kg body weight/day showed further improvement in their activities.
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PMID:Butyric acid modulates activities of intestinal and renal disaccharidases in experimentally induced diabetic rats. 1242 51

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 development of immune-mediated diabetes in BB rats may involve a defect of the gastrointestinal tract (GI), as suggested by increased gut permeability. This study aimed at measuring invertase, maltase, lactase, and peroxidase activities in the duodenum of diabetesprone BioBreeding (BBdp) rats and control BioBreeding rats (BBc) given free access to NIH-07 diet up to the time of killing at 60 66 d of age. After washing the entire small intestine, the duodenal mucosa was scraped off in the first 5-cm segment from the pylorus and frozen in distilled water. Invertase, maltase, and lactase activities were measured by monitoring the conversion of [U-(14)C]sucrose, [U-(14)C]maltose, and [D-[1-(14)C]glucose] lactose to radioactive hexoses, which were phosphorylated in the presence of adenosine triphosphatase and yeast hexokinase and then separated from their precursor by ion-exchange chromatography. Peroxidase activity was measured by a spectrophotometric procedure. In the BBdp rats, the activity of invertase, maltase, and lactase averaged, respectively, 70.2 +/- 4.4, 81.2 +/- 4.3, and 75.7 +/- 4.1% (n = 16 and p < 0.001 in all cases) of the control values found in BBc rats of the same sex. Inversely, after exclusion of two female BBc rats with abnormally high plasma D-glucose concentration, the activity of peroxidase in the BBdp rats averaged 157.4 +/- 20.0% (n = 16; p < 0.02) of the mean control value recorded in BBc rats of the same sex (100.0 +/- 9.3%; n = 14). These findings are compatible with the view that a proinflammatory state of the GI associated with compromise function may precede the occurrence of pancreatic insulitis in BBdp rats and, possibly, human subjects with type 1 diabetes.
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PMID:Invertase, maltase, lactase, and peroxidase activities in duodenum of BB rats. 1262 29

The purpose of this study was to examine the short-term effects of 75, 100 and 150 mg of acarbose mixed in 100 g standard laboratory chow on specific intestinal disaccharidase activities and on hyperglycaemia in diabetic CBA strain mice on standard diet. The small intestine was excised and divided into three segments, from pylorus to duodenum, and two equal lengths of the jejunum and ileum of control and diabetic mice with or without added acarbose. Specific maltase and sucrase activities were determined using maltose and sucrose as substrates respectively. Increased specific activities of maltase and sucrase were detected in the intestines of CBA mice on standard laboratory diet seven days after alloxan-induced diabetes. Feeding for 7 days with 75, 100 or 150 mg acarbose uniformly mixed in 100 g standard laboratory chow, induced a decrease in the specific maltase and sucrase activities, compared with diabetic mice on standard laboratory diet. Feeding with 75 mg acarbose mixed in 100 g standard laboratory chow caused a statistically significant decrease of maltase in the duodenum and of sucrase in duodenum and jejunum, without a antihyperglycaemic effect. Feeding with 100 or 150 mg caused statistically significant decreases in specific maltase and sucrase activities in duodenum, jejunum and ileum. An antihyperglycaemic effect was observed only in the group of diabetic mice fed with 100 mg acarbose. This indicates that the antihyperglycaemic effect of acarbose involves factors other than these, related only to its inhibitory effect on disaccharidase activities.
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PMID:Short-term effect of acarbose on specific intestinal disaccharidase activities and hyperglycaemia in CBA diabetic mice. 1286 6


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