Effects of chemical sympathectomy on insulin receptors and insulin action in isolated rat adipocytes

HG Joost and SH Quentin

Insulin receptors and effects of insulin on lipolysis, lipogenesis and glucose transport were investigated in fat cells obtained from rats chemically sympathectomized with 6-hydroxydopamine. Four days after a single injection of 6-hydroxydopamine (50 mg/kg), the norepinephrine content of the epididymal adipose tissue was reduced by 97.5%. The number of high-affinity insulin binding sites was increased moderately (16%). In parallel, the sensitivity to insulin of the isoprenaline- stimulated lipolysis was increased as judged from insulin concentrations yielding half-maximal inhibition which were lower (40%) in the treated group. Glucose metabolism, however, was inhibited by chemical sympathectomy: the glucose transport rate was significantly reduced and fatty acid synthesis was nearly totally abolished. Insulin was still effective in stimulating both parameters but failed to restore normal levels. The results suggest that the sympathetic innervation of adipose tissue may exert an inhibitory effect on the number of high-affinity insulin receptors as well as on the sensitivity of the lipolysis to insulin, as both parameters were increased by sympathectomy. To explain the inhibitory effect of 6-hydroxydopamine treatment on glucose transport and fatty acid synthesis, a possible trophic effect of the sympathetic innervation is discussed as well as indirect mechanism counteracting the effects of the chemical sympathectomy.

Volume 229, Issue 3, pp. 839-844, 06/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics