Insulin inhibits peroxisomal fatty acid oxidation in isolated rat hepatocytes.
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 (IC(50) = 8.5 x 10(-11) M) at hormone concentrations 100-fold less than those needed for mitochondrial inhibition (IC(50) = 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.
Hamel
F G
FG
Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA. fghamel@unmc.edu
Bennett
R G
RG
Upward
J L
JL
Duckworth
W C
WC
D000214:Acyl Coenzyme A / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D022781:Hepatocytes / Q000648:ultrastructure*; D007328:Insulin / Q000494:pharmacology*; D007339:Insulysin / Q000276:immunology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D000214:Acyl Coenzyme A; D000911:Antibodies, Monoclonal; D005227:Fatty Acids; D007328:Insulin; D019308:Palmitic Acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D007339:Insulysin