Increased lipogenic capacity of the islets of obese rats: A role in the pathogenesls of NIDDM

Young Lee, Hiroshi Hirose, Yan Ting Zhou, Victoria Esser, J. Denis McGarry, Roger H. Unger

研究成果: Article査読

175 被引用数 (Scopus)


The onset of NIDDM in obese Zucker diabetic fatty (fa/fa) rats is preceded 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 β-cell cell function. To determine if the triglyceride accumulation is entirely the passive consequence of high plasma FFA levels or if prediabetic islets have an increased lipogenic capacity that might predispose to NIDDM, the metabolism of long-chain fatty acids was compared in islets of obese prediabetic and nonprediabetic Zucker diabetic fatty (ZDF) rats and 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 [14C]palmitate and 9,10-[3H]palmitate was increased in islets of male obese rats and could not be accounted for by defective oxidation of 9,10-[3H]-palmitate. Glycerol-3-PO4 acyltransferase (GPAT) activity was 12 times that of controls. The mRNA of GPAT was increased in islets of obese rats. We conclude that, in the presence of comparable elevations in FFA concentrations, the islets of obese prediabetic rats have a higher lipogenic capacity than controls. This could be a factor in their high risk of diabetes.

出版ステータスPublished - 1997 3月

ASJC Scopus subject areas

  • 内科学
  • 内分泌学、糖尿病および代謝内科学


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