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| Content Provider | PubMed Central |
|---|---|
| Author | Upton, R. Widdowson, P. S. Ishii, S. Tanaka, H. Williams, G. |
| Copyright Year | 1998 |
| Abstract | We examined the effect of chronic (21 days) oral treatment with the thiazolidinedione, MCC-555 ((±)-5-[{6-(2-fluorbenzyl)-oxy-2-naphy}methyl]-2,4-thiazolidinedione) on metabolic status and insulin sensitivity in obese (fa/fa) Zucker rats and Zucker Diabetic Fatty (ZDF) rats which display an impaired glucose tolerance (IGT) or overt diabetic symptoms, respectively. MCC-555 treatment to obese Zucker rats (10 and 30 mg kg−1) and diabetic ZDF rats (10 mg kg−1) reduced non-esterified fatty acid concentrations in both rat strains and reduced plasma glucose and triglyceride concentrations in the obese Zucker rats. Liver glycogen concentrations were significantly increased by chronic MCC-555 treatment in both obese Zucker rats (30 mg kg−1 day−1) and diabetic ZDF rats (10 mg kg−1 day−1), as compared with vehicle-treated lean and obese rats and there was a significant increase in hepatic glycogen synthase activity in MCC-555-treated diabetic ZDF rats as compared to vehicle-treated controls. During a euglycaemic hyperinsulinaemic clamp, MCC-555-treated obese Zucker rats and diabetic ZDF rats required significantly higher glucose infusion rates to maintain stable glucose concentrations (2.01±0.19 mg min−1 and 6.42±1.03 mg min−1, respectively) than vehicle-treated obese controls (0.71±0.17 mg min−1 and 2.09±0.71 mg min−1; P<0.05), demonstrating improved insulin sensitivity in both Zucker and ZDF rats. MCC-555 treatment also enhanced insulin-induced suppression of hepatic glucose production in ZDF rats as measured using infusions of [6-3H]-glucose under clamp conditions. In conclusion, we have demonstrated that MCC-555 improves metabolic status and insulin sensitivity in obese Zucker and diabetic ZDF rats. MCC-555 may prove a useful compound for alleviating the metabolic disturbances and IGT associated with insulin resistance in man. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0702245 |
| Ending Page | 1714 |
| Page Count | 7 |
| Starting Page | 1708 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 8 |
| Volume Number | 125 |
| Language | English |
| Publisher Date | 1998-12-01 |
| Access Restriction | Open |
| Subject Keyword | Pharmacology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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