Desensitization of beta-adrenergic receptors in adipocytes causes increased insulin sensitivity of glucose transport

To determine the effect of desensitization of adipocyte beta-adrenergic receptors on insulin sensitivity, rats were continuously infused with isoproterenol (50 or 100 mu g . kg(-1). h(-1)) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treated animals were desensitized to isoproterenol, as determined by response of lipolysis (glycerol release). Binding of [I-125]iodocyanopindolol was decreased by similar to 80% in adipocyte plasma membranes isolated from treated rats, indicating that p-adrenergic receptors were downregulated. Cellular concentrations of G(s) alpha and G(i)a were not altered. Insulin sensitivity was determined by measuring the effect of insulin on glucose transport (2-deoxy-[H-3]glucose uptake). Cells from the 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 half-maximal effective concentration of insulin in both groups. I-125-labeled insulin binding to adipocytes was not altered by the isoproterenol infusions, indicating that desensitization of beta-adrenergic receptors results in tighter coupling between insulin receptors and stimulation of glucose transport.