Adenosine and prostaglandins of the E series inhibit lipolysis in adipocytes by binding to cell surface receptors. This inhibition is mediated via Gi. It has been reported that Gi is almost absent in livers from diabetic rats. Therefore, we have evaluated the sensitivity of adipocytes from diabetic rats to the adenosine analogue N6-phenylisopropyl adenosine (PIA) and to prostaglandin E1 (PGE1). Diabetes was induced with streptozocin (65 mg/kg i.v.), and after 7 days, adipocytes were isolated. Lipolysis (measured in the presence of adenosine deaminase) was inhibited by PIA and PGE, in both control and diabetic cells. However, the dose-response curves were markedly shifted to the right in the cells from diabetic rats. The IC50 for PIA was 0.30 ± 0.02 nM in controls and 0.83 ± 0.08 in diabetic rats (P < 0.001), and the IC50 for PGE, was 3.16 ± 0.18 nM in controls and 5.26 ± 0.57 nM in diabetic rats (P < 0.02). These findings indicate decreased sensitivity to both adenosine and PGE1. Adipocyte membranes were isolated from control and diabetic rats. Adenosine receptors (measured by binding of 125I-labeled hydroxy-PIA) were not altered in cells from diabetic rats. However, the ability of Gpp(NH)p (a nonhydrolyzable GTP analogue) to inhibit adenosine-receptor binding was markedly decreased in membranes from diabetic rats, suggesting a change at the level of G1. The α-subunits of G11, G12, G13, and Gs were quantitated on Western blots with a series of recently characterized anti-peptide antisera. This revealed that the amounts of each of these G proteins were normal in membranes from the diabetic rats. These findings suggest that there is a functional but not quantitative abnormality in G1 in adipocytes from diabetic rats that results in abnormal coupling of both A1-adenosine receptors and prostaglandin receptors and would explain the decreased sensitivity to PIA and PGE1.
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Original Articles| January 01 1991
Evidence for Impaired Coupling of Receptors to Gi Protein in Adipocytes From Streptozocin-Induced Diabetic Rats
Address correspondence and reprint requests to Allan Green, PhD, Department of Internal Medicine, Route E-68, University of Texas Medical Branch, Galveston, TX 77550.
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Allan Green, Jeff L Johnson; Evidence for Impaired Coupling of Receptors to Gi Protein in Adipocytes From Streptozocin-Induced Diabetic Rats. Diabetes 1 January 1991; 40 (1): 88–94. https://doi.org/10.2337/diab.40.1.88
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