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Am J Physiol Endocrinol Metab 271: E742-E747, 1996;
0193-1849/96 $5.00
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AJP - Endocrinology and Metabolism, Vol 271, Issue 4 E742-E747, Copyright © 1996 by American Physiological Society


ARTICLES

Prevention of hyperglycemia in the Zucker diabetic fatty rat by treatment with metformin or troglitazone

S. Sreenan, J. Sturis, W. Pugh, C. F. Burant and K. S. Polonsky
Department of Medicine, University of Chicago, Illinois 60637, USA.

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 perfused pancreas were measured. Metformin-treated rats gained significantly less weight. Both drugs prevented hyperglycemia by 12 wk in diabetic rats and significantly reduced TG and FFA levels. Insulin secretion at low glucose was elevated in untreated fatty and diabetic animals, and the increment in diabetic animals produced by glucose perfusion was attenuated compared with lean and fatty rats. Both drugs reduced basal insulin secretion in fatty and diabetic rats and improved glucose responsiveness in diabetic rats. Metformin and troglitazone delay the onset of diabetes in the ZDF rat. The significantly improved insulin secretory response of the pancreas undoubtedly contributes to the improved glucose tolerance.


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