PREVENTION OF HYPERGLYCEMIA IN THE ZUCKER DIABETIC FATTY RAT BY TREATMENT WITH METFORMIN OR TROGLITAZONE

To determine whether metformin or troglitazone can delay the onset of diabetes in the Zucker diabetic fatty (ZDF) rat, lean control, fatty, and ZDF rats received metformin, troglitazone, or no treatment from 6 to 12 wk. of age. Glucose, insulin, triglyceride (TG), and free fatty acid (FFA) levels and glucose-stimulated insulin secretion by the perf used pancreas were measured. Metformin-treated rats gained significant ly less weight. Both drugs prevented hyperglycemia by 12 wk in diabeti c rats and significantly reduced TG and FFA levels. Insulin secretion at low glucose was elevated in untreated fatty and diabetic animals, a nd the increment in diabetic animals produced by glucose perfusion was attenuated compared with lean and fatty rats. Both drugs reduced basa l insulin secretion in fatty and diabetic rats and improved glucose re sponsiveness in diabetic rats. Metformin and troglitazone delay the on set of diabetes in the ZDF rat. The significantly improved insulin sec retory response of the pancreas undoubtedly contributes to the improve d glucose tolerance.