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.
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Original Articles|
March 01 1997
Increased Lipogenic Capacity of the Islets of Obese Rats: A Role in the Pathogenesis of NIDDM
Young Lee;
Young Lee
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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Hiroshi Hiros;
Hiroshi Hiros
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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Yan-Ting Zhou;
Yan-Ting Zhou
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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Victoria Esser;
Victoria Esser
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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J Denis McGarry;
J Denis McGarry
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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Roger H Unger
Roger H Unger
Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center
Dallas
; and Department of Veterans Affairs Medical Center
Dallas, Texas
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Address correspondence and reprint requests to Roger H. Unger, MD, Center for Diabetes Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235–8854.
1
ACO, acyl-CoA oxidase; ANOVA, analysis of variance; B-ACS, acyl-CoA synthetase; BSA, bovine serum albumin; CPT-1, carnitine palmitoyl transferase I; FFA, free fatty acid; GPAT, glycerol-3-PO4 acyltransferase; L-ACS, acyl-CoA synthetase; NO, nitric oxide; RT-PCR, reverse transcription–polymerase chain reaction; ZDF, Zucker diabetic fatty.
Diabetes 1997;46(3):408–413
Article history
Received:
December 20 1995
Revision Received:
October 02 1996
Accepted:
October 02 1996
PubMed:
9032096
Citation
Young Lee, Hiroshi Hiros, Yan-Ting Zhou, Victoria Esser, J Denis McGarry, Roger H Unger; Increased Lipogenic Capacity of the Islets of Obese Rats: A Role in the Pathogenesis of NIDDM. Diabetes 1 March 1997; 46 (3): 408–413. https://doi.org/10.2337/diab.46.3.408
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