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Endocrinology Vol. 142, No. 6 2702-2706
Copyright © 2001 by The Endocrine Society

ARTICLES

Insulin Inhibits Peroxisomal Fatty Acid Oxidation in Isolated Rat Hepatocytes1

Frederick G. Hamel2, Robert G. Bennett2, Jennifer L. Upward and William C. Duckworth

Research Service (F.G.H., R.G.B., J.L.U.), Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105; Department of Internal Medicine (F.G.H., R.G.B.), Department of Pharmacology (F.G.H.), University of Nebraska Medical Center, Omaha, Nebraska 68198; and Carl T. Hayden Medical Center (W.C.D.), Department of Veterans Affairs, Phoenix, Arizona 85012

Address all correspondence and requests for reprints to: Frederick G. Hamel, Ph.D., Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, Nebraska 68105.

Inhibition by insulin of long chain fatty acid oxidation in mitochondria is mediated in part by elevating malonyl-CoA levels, which inhibit carnitine palmitoyl-transferase I. Whether insulin alters peroxisomal oxidation has not been studied. We present data which show that insulin inhibits the oxidation of palmitic acid by peroxisomes (IC50 = 8.5 x 10-11 M) at hormone concentrations 100-fold less than those needed for mitochondrial inhibition (IC50 = 1.3 x 10-8 M). We used a purified peroxisome preparation to study the mechanism of insulin action. Insulin had a direct effect in the peroxisome preparations to decrease oxygen consumption, fatty acyl-CoA oxidizing system activity and acyl-CoA oxidase by approximately 40%, 30% and 15%, respectively. Since insulin degrading enzyme (IDE) is an insulin-binding protein known to be in peroxisomes, we studied the effect of an inhibitory anti-IDE antibody on the ability of insulin to inhibit the fatty acyl-CoA oxidizing system. The antibody eliminated the inhibitory effect of insulin. We conclude that insulin inhibits peroxisomal fatty acid oxidation by a mechanism requiring IDE.






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Copyright © 2001 by The Endocrine Society