INCREASED LIPOGENIC CAPACITY OF THE ISLETS OF OBESE RATS - A ROLE IN THE PATHOGENESIS OF NIDDM

The onset of NIDDM in obese Zucker diabetic fatty (fa/fa) rats is prec eded by a striking increase in the plasma levels of free fatty acids ( FFAs) and by a sixfold rise in triglyceride content in the pancreatic islets, The latter finding provides clear evidence of elevated tissue levels of long-chain fatty acyl CoA, which can impair beta-cell cell f unction, To determine if the triglyceride accumulation is entirely the passive consequence of high plasma FFA levels or if prediabetic islet s have an increased lipogenic capacity that might predispose to NIDDM, the metabolism of long-chain fatty acids was compared in islets of ob ese prediabetic and nonprediabetic Zucker diabetic fatty (ZDF) rats an d of lean Wistar and lean ZDF rats, When cultured in 1 or 2 mmol/l FFA , islets of both female and male obese rats accumulated, respectively, 7 and 15 times as much triglyceride as islets from lean rats exposed to identical FFA concentrations, The esterification of [C-14]palmitate and 9,10-[H-3]palmitate was increased in islets of male obese rats an d could not be accounted for by defective oxidation of 9,10-[H-3]-palm itate. Glycerol-3-PO4 acyltransferase (GPAT) activity was 12 times tha t of controls, The mRNA of GPAT was increased in islets of obese rats, We conclude that, in the presence of comparable elevations in FFA con centrations, the islets of obese prediabetic rats have a higher lipoge nic capacity than controls. This could be a factor in their high risk of diabetes.