DESENSITIZATION OF BETA-ADRENERGIC RECEPTORS IN ADIPOCYTES CAUSES INCREASED INSULIN SENSITIVITY OF GLUCOSE-TRANSPORT

To determine the effect of desensitization of adipocyte beta-adrenergi c receptors on insulin sensitivity, rats were continuously infused wit h isoproterenol (50 or 100 mu g . kg(-1). h(-1)) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treate d animals were desensitized to isoproterenol, as determined by respons e of lipolysis (glycerol release). Binding of [I-125]iodocyanopindolol was decreased by similar to 80% in adipocyte plasma membranes isolate d from treated rats, indicating that p-adrenergic receptors were downr egulated. Cellular concentrations of G(s) alpha and G(i)a were not alt ered. Insulin sensitivity was determined by measuring the effect of in sulin on glucose transport (2-deoxy-[H-3]glucose uptake). Cells from t he isoproterenol-infused rats were markedly more sensitive to insulin than those from control rats. This was evidenced by an similar to 50% increase in maximal glucose transport rate in cells from the high-dose isoproterenol-treated rats and by an similar to 40% decrease in the h alf-maximal effective concentration of insulin in both groups. I-125-l abeled insulin binding to adipocytes was not altered by the isoprotere nol infusions, indicating that desensitization of beta-adrenergic rece ptors results in tighter coupling between insulin receptors and stimul ation of glucose transport.