Insulin inhibits peroxisomal fatty acid oxidation in isolated rat hepatocytes

Frederick G. Hamel, Robert G. Bennett, Jennifer L. Upward, William C. Duckworth

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 × 10-11 M) at hormone concentrations 100-fold less than those needed for mitochondrial inhibition (IC50 = 1.3 × 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.

Original languageEnglish (US)
Pages (from-to)2702-2706
Number of pages5
JournalEndocrinology
Volume142
Issue number6
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Endocrinology

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