Insulin resistance in adipocytes after down-regulation of gi subtypes with n6-phenylisopropyl adenosine or prostaglandin e1. Green, Allan, Diedra J. A. Walters, and Susan B. Dobias. Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555
APStracts 4:0076E, 1997.
To determine whether down-regulation of Gi-proteins is associated with insulin resistance, we incubated isolated adipocytes with N6 -phenylisopropyl adenosine (PIA; an A1-adenosine receptor agonist) (300 nM), PGE1 (3 (M), or nicotinic acid (1 mM) for 4 days in primary culture. The cells were washed, and the rate of glucose transport (2 -deoxy [3H]glucose uptake) was measured after incubation with various concentrations of insulin for 45 min. Both PIA and PGE1 (which down -regulate Gi) decreased the maximal responsiveness of the cells to insulin by about 30% and caused a rightward shift in the dose -response curve. By contrast, nicotinic acid (which does not down -regulate Gi) did not alter the insulin sensitivity of the cells. Prolonged treatment of adipocytes with either PIA or PGE1 (but not nicotinic acid) rendered the cells completely resistant to the antilipolytic effect of insulin. The ability of insulin to stimulate autophosphorylation of the (-subunit of the insulin receptor was decreased by about 30% in PIA-treated cells, and the dose-response curve was shifted to the right. Similarly, the ability of the receptor to phosphorylate poly (Glu4-Tyr1) was decreased by about 35%. This decrease in tyrosine kinase activity of the receptor may account for the decrease in insulin sensitivity of glucose transport, but cannot account for the complete loss of antilipolysis. The findings suggest both a direct and indirect involvement of Gi -proteins in insulin action. 

Received 21 October 1996; accepted in final form 27 March 1997.
APS Manuscript Number E527-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 3 April 1997