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pharmacol.usyd.edu.au
1. The recent development of a series of novel KATP channel modulators, namely sulphonylthioureas and sulphonylureas, is thought to make improvements in potency and tissue selectivity compared with current sulphonylureas, such as glibenclamide, which shares a similar structure to the novel compounds. 2. These novel compounds were first examined for their effect on hyperglycaemia and glucose tolerance during an oral glucose tolerance test following 5 days administration in the lean fa/- and obese fa/fa Zucker rat (a model of insulin resistance). Comparisons with present antidiabetic agents, metformin and glibenclamide were performed. 3. Several compounds showed improvements in glucose tolerance compared with control and the primary structural prerequisites for the maintenance of this activity were investigated. Of most interest was compound 3-15 ((N-[(4-methylphenylsulphonyl]-N'-(2-ethoxypyrid-4-yl)thiourea; 0.1 mg/kg per day), which significantly improved glucose tolerance following 5 days administration in the fa/fa Zucker rat. This paralleled the improvement seen in metformin (300 mg/kg per day)-treated fa/fa rats, but compound 3-15 was up to 3000-fold more potent than metformin. 4. Obese fa/fa Zucker rats were then treated with compound 3-15 for 28 days to determine whether glycaemic control could be maintained over the longer term. 5. Compound 3-15 showed a significant improvement in glucose clearance and reduction in insulin concentration following 28 days treatment during an intravenous glucose tolerance test compared with untreated rats, without any change in the rate of weight gain. 6. The novel sulphonylthiourea 3-15 appears to improve glucose clearance during acute and chronic treatment in the fa/fa Zucker rat with no effect on the rate of weight gain. It is thought that compound 3-15 may be eliciting its actions by improving insulin sensitivity, but its effects on insulin secretion are still to be elucidated.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11380511&dopt=Abstract
J Ethnopharmacol. 1996 Jan;50(1):43-7.
Effect of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) extracts on blood glucose level of normal and streptozotocin diabetic rats.
El-Fiky FK, Abou-Karam MA, Afify EA.
Department of Phalmacognosy, University of Alexandria, Egypt.
The present study investigates the effect of oral administration of the ethanolic extracts of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) on blood glucose levels both in normal and streptozotocin (STZ) diabetic rats. Treatment with both extracts significantly reduced the blood glucose level in STZ diabetic rats during the first three hours of treatment. L. aegyptiaca extract decreased blood glucose level with a potency similar to that of the biguanide, metformin. The total glycaemic areas were 589.61 +/- 45.62 mg/dl/3 h and 660.38 +/- 64.44 mg/dl/3 h for L. aegyptiaca and metformin, respectively, vs. 816.73 +/- 43.21 mg/dl/3 h for the control (P < 0.05). On the other hand, in normal rats, both treatments produced insignificant changes in blood glucose levels compared to glibenclamide treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8778506&dopt=Abstract
paradigm.nl
OBJECTIVE: The aim of this study was to estimate the effect of metformin on the serum total homocysteine level in non-insulin-dependent diabetes mellitus (NIDDM) patients. An elevated serum total homocysteine level is a risk factor for atherosclerosis. Metformin decreases serum vitamin B12, and may thereby indirectly increase the serum total homocysteine level. DESIGN: A cross-sectional study in a primary care setting. SUBJECTS, MAIN OUTCOME MEASURES: Fasting serum total homocysteine level was measured in 40 NIDDM patients who had received treatment with metformin (500-2550 mg per day) for at least six months, and in 71 NIDDM patients not treated with metformin and matched for sex, age (+/- 5 years), serum creatinine (+/- 5 micromol L[-1]) and current smoking habits. 'Exposed' patients were matched with 'nonexposed' patients. A two-way analysis of variance was performed. RESULTS: The mean serum total homocysteine level was 11.5 micromol L(-1) in the metformin-exposed patients and 10.6 micromol L(-1) in the nonexposed patients. Thus, the metformin-exposed patients had slightly higher serum total homocysteine levels (difference 0.8 micromol L(-1), 95% confidence interval (-0.4-2.0 micromol L[-1]). Results were similar in men and women. Finally, no dose-response relationship between cumulative exposure to metformin (dose x duration of treatment) and the serum total homocysteine level could be demonstrated. CONCLUSION: We conclude that the effect of metformin on serum total homocysteine level in NIDDM patients, if any, is likely to be small.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9408068&dopt=Abstract
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