Influence of aging on the effect of troglitazone on serum lipid levels and glucose tolerance in insulin-resistant Zucker fatty rats

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.158-158
• Main Authors: Makita, Yumi, Unakami, Satoshi, Iizuka, Hiromi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34647-5

Zucker fatty rats being phenotypically obese, exhibit hyperlipidemia, hyperinsulinemia and decrease in glucose tolerance in comparison with the lean rats of the same strain. To examine age difference, effect of troglitazone on the serum lipids, insulin levels and glucose tolerance were investigated in Zucker fatty rats at 18, 28 and 54 weeks of age. Peak value of the serum insulin level was observed at 18 weeks of age and the value was over 4-times higher than that of the other ages. Age-dependent elevation were observed in serum VLDL-triglyceride and LDL-cholesterol levels, however, no age dependency were observed in serum HDL-cholesterol, free fatty acid, leptin levels and glucose tolerance. After oral administration of troglitazone at 50 mg/kg twice a day for 2 weeks, the fatty rats showed the normalization of serum insulin, VLDL-triglyceride and free fatty acid levels at all ages. On glucose tolerance, troglitazone improved its ability at 18 weeks of age, but not at the other ages. These results indicate that age difference in the improving effect of glucose tolerance in Zucker fatty rats may be associated with an altered sensitivity to the antidiabetic actions of troglitazone.