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At least 811 records · Page 45Linked to original sources
PubMed1981

The antidiabetic effect and pharmacokinetic properties of glipizide. Comparison of a single dose with divided dose regime.

In 13 patients with maturity-onset diabetes mellitus which did not respond to diet therapy alone, serum concentration of glipizide, blood glucose (B-G) concentration, serum immunoreactive insulin (S-IRI) and plasma glycerol (P-G) were monitored hourly over 12 hours after placebo, an initial dose of glipizide (5 mg p.o.) and long-term treatment with glipizide (range 7.5--20 mg, mean 10.4), which produced fasting B-G of less than 8 mmol/l. During the long-term treatment, glipizide was given in a random, cross-over pattern, either as a single dose in the morning or as a three-part divided dose regime, in the same total daily amount. The duration of the immediate effects of glipizide on B-G, S-IRI and S-IRI/B-G was 9, 4.5 and 6.5 hours, respectively. The mean apparent half-life of glipizide was 4.1 hours, the mean distribution volume 0.13 l/kg and the mean plasma clearance 0.023 l/kg x h. The area under the concentration curve from 7.30 a.m. to 7.30 p.m. was 15% higher after the single dose regime. The serum levels of glipizide at 10 hours were only 30% lower than after the three-part divided dose regime. There were no significant differences between the single and divided dose regimes as regards B-G, S-IRI and S-IRI/B-G, although the mean B-G for the 12-hour period was somewhat lower after the former than after the latter (7.0 against 8.7 mmol/l).

Aged↗
PubMed2004

Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin and hepatic enzymes of glucose metabolism in hyperglycaemic rats.

AIM: The present study was designed to investigate the effect of diasulin, a polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in this study. The rats were divided into seven groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1: normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10 g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of glibenclamide (600 micro g/kg of body weight). The treatment was given for 30 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with diasulin resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in plasma insulin and total haemoglobin and a significant improvement in glucose tolerance. Diasulin also resulted in a significant reduction in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity was significantly increased in alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that diasulin, a polyherbal drug, controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible, because it regulates the activities of hepatic glucose metabolic enzymes.

Analysis of Variance↗
PubMed1989

Effect of oral antidiabetic drug withdrawal in type 2 diabetes.

Oral hypoglycaemic agents were withdrawn in 22 Type 2 diabetic patients to establish whether long-term use of these products is really necessary. Discontinuation of the drugs resulted in significant increases of HbA1 (8.1 +/- 1.1 to 11.3 +/- 2.4%) and fasting (9.1 +/- 2.1 to 13.6 +/- 4.0 mmol l-1) and postprandial (12.3 +/- 3.0 to 18.7 +/- 5.7 mmol l-1) plasma glucose levels after 12 weeks (all p less than 0.01). This was associated with a reduction of fasting (12.4 +/- 6.2 to 8.0 +/- 3.4 mU l-1) and postprandial (35.7 +/- 13.2 to 19.3 +/- 13.4 mU l-1) serum insulin concentrations, and fasting (0.8 +/- 0.4 to 0.5 +/- 0.2 nmol l-1) and postprandial (1.8 +/- 0.6 to 1.0 +/- 0.5 nmol l-1) serum C-peptide concentrations (all p less than 0.01). Only one patient did not show metabolic deterioration after drug withdrawal. In multivariate analysis no significant correlations could be found between measures of baseline diabetic control and the deterioration after drug withdrawal.

Aged↗
PubMed1959

Mechanism of action of oral antidiabetic drugs.

The fall in blood sugar with carbutamide (BZ55) 24 hr. after the maintenance dose of insulin (28.1%+/-2.9 s.e) in rabbits made severely diabetic with alloxan was significantly different from the change in the blood sugar with the same drug given 72 hr. (6.8%+/-2.0) or distilled water given 24 hr. (7.7%+/-1.3) respectively after the last dose of insulin. It is postulated that the drug acts by liberating bound insulin in the plasma.

Alloxan↗
PubMed1979

Improved insulin receptor assay: effects of an antidiabetic sulphonylurea on liver membrane insulin receptors from obese hyperglycaemic mice.

1 A simple assay of liver membrane insulin receptors is described, under conditions which apparently stabilized the insulin-receptor complex. The receptor population was measured in the presence of physiological doses of radioactive hormone under conditions which minimized negative co-operativity effects. 2 Equilibrium between receptor and hormone was attained in vitro within 60 min of incubation time at 13 degrees C with no apparent loss of binding sites after 3 h of incubation. 3 Liver membranes from lean mice possessed 8.8 times the receptor number per mg membrane protein measured in membranes from obese hyperglycaemic (ob/ob) littermates. After treatment of ob/ob mice with ARDF-26 (Gliquidon; Boehringer Ingelheim Ltd) the concentration of liver membrane insulin receptors was increased 5 fold.

Animals↗
PubMed1997

Antidiabetic efficacy of BRL 49653, a potent orally active insulin sensitizing agent, assessed in the C57BL/KsJ db/db diabetic mouse by non-invasive 1H NMR studies of urine.

High resolution 1H nuclear magnetic resonance (NMR) spectroscopic analysis of biofluids is a recently established tool for evaluating inherited and acquired errors in metabolic control. In the present study 1H NMR analysis of urine was used to monitor efficacy of BRL 49653, a potent and selective antihyperglycaemic agent, following oral administration for up to 36 weeks to the genetically diabetic C57BL/KsJ db/db mouse. The effects of BRL 49653 on carbohydrate and fatty acid metabolism were monitored by determination of changes in concentrations of low molecular weight urinary metabolites. A qualitative comparison of the NMR spectra of urine from untreated diabetic mice with those of lean littermates and literature examples revealed several abnormalities, the majority of which could be explained in terms of the non-insulin dependent diabetes syndrome exhibited by these animals. Quantitatively the most prominent was the extreme glycosuria of both young (8-12 weeks; 0.9 g glucose kg-1 h-1) and older (42 weeks; 2 g glucose kg-1 h-1) diabetic mice. This was accompanied by the excretion of a number of unassigned sugar derivatives and by ketone bodies. Administration of BRL 49653 (3 mumol kg-1) to db/db mice for 24 days reduced blood glucose concentrations to values comparable with non-diabetic lean littermates and reduced glycosuria by > 90%. BRL 49653 significantly reduced excretion of unassigned sugars, acetate, lactate, and the ketone bodies, acetoacetate, 3-D-hydroxybutyrate and acetone. The anti-diabetic efficacy of BRL 49653, assessed from the pattern of urinary metabolites, was maintained over a 36-week treatment period. These results demonstrate the value of 1H NMR to evaluate non-invasively the efficacy of novel therapeutic agents.

Administration, Oral↗