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

Post-prandial glucose excursions remain elevated in most patients with diabetes even when normal fasting plasma glucose levels have been achieved. In 39 patients with type 2 diabetes who had attained basal normoglycaemia by therapy with diet alone, a sulphonylurea, a basal insulin supplement or basal plus prandial insulin the mean glycosylated haemoglobin (HbA1) values were at the upper end (mean +/- 1SD, 8.1 +/- 1.1%) of the normal range (5.0-8.2%). Miglitol, an alpha-glucosidase inhibitor, given in a dose of 50 mg three times a day was studied in a double blind randomized crossover study. In diet and sulphonylurea treated patients, a mean 25% reduction of the post-prandial plasma glucose excursions was obtained whereas in ultralente treated patients miglitol appeared to reduce basal plasma glucose levels (p < 0.006). Side effects were limited to minor gastrointestinal disturbances, usually ameliorating after the first week of therapy. Alpha-glucosidase inhibition to prevent post-prandial glycaemia may have a role in patients in whom sulphonylurea or diet therapy has been used to obtain normal basal glucose concentrations.
Diabetes Res 1991 Dec
PMID:Post-prandial glycaemic reduction by an alpha-glucosidase inhibitor in type 2 diabetic patients with therapeutically attained basal normoglycaemia. 184 49

1. The effect of the alpha-glucosidase inhibitor Acarbose on integrated glycemic control and on nonenzymatic glycation of glomerular basement membrane was examined in streptozotocin diabetic rats. 2. Treatment with Acarbose for 8 weeks after induction of diabetes significantly reduced the level of HbA1c and of glomerular basement membrane glycation. 3. Acarbose exerts a significant antihyperglycemic effect and has a salutary influence on the nephropathic process in experimental diabetes.
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PMID:Effect of alpha-glucosidase inhibition on the nonenzymatic glycation of glomerular basement membrane. 186 25

1. The effect of the alpha-glucosidase inhibitor Acarbose on collagen fluorescence reflecting formation of advanced glycation end products was examined in streptozotocin-diabetic rats. 2. Treatment with Acarbose for eight weeks after induction of diabetes prevented the increased fluorescence in skin and tail tendon collagen associated with untreated diabetes. 3. Acarbose improves integrated glycemic control and beneficially influences the consequences of excess glycation in long-lived connective tissue proteins.
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PMID:Alpha-glucosidase inhibition prevents increased collagen fluorescence in experimental diabetes. 193 95

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

The influences of glucose, the benzothiadiazide derivative diazoxide (an inhibitor of insulin release), and the potent non-glucose insulin secretagogue 3-isobutyl-1-methylxanthine (IBMX) on insulin secretion and the activities of 3 different lysosomal enzymes were studied in isolated mouse islets. We found that the increase in insulin secretion during a 4 hr incubation period in the presence of 16.7 mM glucose was accompanied by an increase in islet activities of the lysosomal enzymes acid amyloglucosidase and acid alpha-glucosidase. These alpha-1,4-glucoside splitting enzyme activities were increased by 45-55% (p less than 0.01). No influence by glucose was encountered for the activities of N-acetyl-beta-D-glucosaminidase or the non-lysosomal neutral alpha-glucosidase. Upon incubation with 0.2 mM diazoxide and glucose (16.7 mM) the glucose-induced insulin secretion was markedly suppressed and no significant increase in islet lysosomal enzyme activities was observed. On the other hand, insulin secretion induced by IBMX to the same magnitude as with 16.7 mM glucose, was accompanied by an increase in islet activity of N-acetyl-beta-D-glucosaminidase (p less than 0.05), whereas no apparent changes in acid amyloglucosidase and acid alpha-glucosidase activities could be detected. In conclusion, the determination of lysosomal enzyme activities in isolated mouse islets revealed that glucose was able to induce an increased activity of glucose producing glycogenolytic acid hydrolases under conditions when a concomitant insulin secretion occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1986 Oct
PMID:Insulin secretion and lysosomal enzyme activities in isolated mouse islets. Effects of glucose, diazoxide and isobutylmethylxanthine. 243 78

The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents. Basal and cerulein-stimulated flow rates of pancreatic juice in rats with the ACS or ACG diet were similar to those in rats fed the control diet, suggesting that the pancreata from rats treated with acarbose have normal sensitivity and responsiveness to cerulein. On the other hand, cerulein-stimulated amylase output was significantly decreased in rats with the ACS diet, but was normal in rats with the ACG diet. Insulin secretion to both glucose and cerulein stimulation in rats fed the ACS diet was reduced by approximately 55% compared with the control rats. On the other hand, rats fed the ACG diet showed normal insulin secretion to glucose stimulation, although the insulin response to cerulein stimulation was reduced by 30%. These results suggest that the addition of acarbose to the sucrose-rich diet decreases the secretory responsiveness of amylase to cerulein stimulation and that of insulin to both glucose and cerulein stimulation. All these alterations, except the sensitivity of B cells to cerulein, can be normalized by replacing sucrose with glucose.
Diabetes Res Clin Pract 1988 Oct 14
PMID:Effect of alpha-glucosidase inhibitor on exocrine and endocrine pancreatic function in rats fed a high-carbohydrate diet consisting of sucrose or glucose. 246 25

The activities of lysosomal maltase in the serum, urine and kidney were determined in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and compared with the changes in N-acetyl-beta-D-glucosaminidase (NAG) activity. Moreover, effects of insulin on maltase and NAG activities of the serum, urine and kidney in diabetic rats were studied. The following results were obtained: 1) The serum maltase activity within 24 hr after administration of STZ was influenced by insulin secretion. 2) Significant increases in blood urea nitrogen (BUN) levels were observed from the 3rd week after a single administration of STZ. The serum insulin level significantly decreased at 3 weeks after treatment of STZ. In this time, maltase activity in the serum rapidly increased, while the enzyme activity in the kidney decreased considerably. On the other hand, the changes in NAG activities in the serum, urine and kidney after administering STZ were almost similar to those in maltase activities. 3) There were positive relationships between maltase and NAG activities in the serum and urine in diabetic rats, respectively. 4) When lente insulin (2U) was subcutaneously injected once daily for 20 days from 24 hr after administration of STZ, NAG activities in the serum and kidney approached to the control levels. However, maltase activities in the group treated with insulin were significantly higher in the serum and kidney than those in the control group.
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PMID:[Effects of insulin on maltase and N-acetyl-beta-D-glucosaminidase (NAG) activities of serum and kidney in experimental diabetic rats]. 253 Jan 41

The effect of the glucose analogue N-hydroxyethyl-1-deoxynojirimycin (BAY m 1099) on the activity of alpha-glucosidases was studied in human fibroblasts and HepG2 cells. BAY m 1099 inhibits neutral and acid alpha-glucosidase activities of both cell types in a dosage-dependent and reversible manner. Inhibition of endoplasmic reticulum glucosidases I and/or II is suggested by delayed processing of lysosomal (acid) alpha-glucosidase. Competitive inhibition of mature acid alpha-glucosidase leads to lysosomal accumulation of glycogen as in glycogenosis type II. There seems to be little risk, however, of inducing this storage disorder when using the drug in a dose of 50 mg per os for treatment of type II diabetes. In high doses, the drug may prove useful for studying the pathogenesis of glycogenosis type II in vitro or in animal models.
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PMID:Effects of N-hydroxyethyl-1-deoxynojirimycin (BAY m 1099) on the activity of neutral- and acid alpha-glucosidases in human fibroblasts and HepG2 cells. 254

The effect of a new alpha-glucosidase inhibitor BAY-M-1099 on postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading was studied. Evaluation was also made of the metabolic consequences of the addition of BAY-M-1099 to a high-carbohydrate diet consisting of equal quantities of wheat starch and sucrose (Diet A). This drug significantly reduced (p less than 0.05) postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading. BAY-M-1099 led to a significant reduction in urinary glucose loss (177.8 +/- 54.2 vs 98.9 +/- 35.6 mmol/L) and in postprandial plasma glucose levels in diabetic rats fed diet A. Addition of BAY-M-1099 to the diet of nondiabetic rats significantly (p less than 0.05) decreased the postprandial plasma glucose level at 45, 90, 180, and 225 min after a meal test. Addition of BAY-M-1099 to a diet containing starch plus sucrose led to reduced glycosuria and serum glucose levels and may have potential benefit in the management of diabetes mellitus.
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PMID:Metabolic consequences of the alpha-glucosidase inhibitor BAY-M-1099 given to nondiabetic and diabetic rats fed a high-carbohydrate diet. 264 91

The SHR/N-corpulent (cp) rat exhibits some of the metabolic characteristics associated with human noninsulin-dependent diabetes mellitus (NIDDM). To determine the effect of the alpha-glucosidase inhibitor, acarbose (BAY-g-5421), on expression of NIDDM in this model, young male obese and lean littermates were fed for 12 wk diets containing either 54% starch, sucrose, or sucrose plus acarbose (150 mg acarbose/kg diet). Body weight; fasting levels of serum triglyceride, total cholesterol, insulin and glucose; response levels of insulin and glucose following an oral glucose tolerance test (OGTT); and total urinary glucose were determined. Supplementation of the sucrose diet with acarbose reduced final body weight in obese rats, as well as serum triglyceride, total cholesterol, response insulin, and urinary glucose in both phenotypes. Glucosuria was normalized in acarbose-treated obese rats. In addition, acarbose improved the glycemic response following OGTT in both phenotypes. These findings demonstrate that acarbose is effective in moderating the metabolic effects of NIDDM in this diabetic rodent model, and suggest that acarbose may have potential in the management of NIDDM in humans.
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PMID:Effect of acarbose (BAY-g-5421) on expression of noninsulin-dependent diabetes mellitus in sucrose-fed SHR/N-corpulent rats. 264 1


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