Decreased glucagon binding and glucagon-stimulated lipolysis in adipocytes from streptozotocin-diabetic rats

Adipocytes from streptozotocin-diabetic rats showed a markedly reduced lipolytic response to glucagon concomitant with a 90% or greater decrease in the number of glucagon receptors per cell. In contrast, beta-adrenergic receptors assessed by [3H]dihydroalprenolol binding and lipolysis stimulated by isoproterenol, dibutyryl 3'5'-cyclic AMP and 3-isobutyl-1-methylxanthine were reduced by only 10-25% in diabetic rats compared with controls. Furthermore, quantitative analysis of the relationship between the amount of cell-bound glucagon and the hormone-stimulated lipolysis revealed that the function of the remaining 10% of glucagon receptors remained intact in cells from diabetic animals. These findings suggest that the lipolytic cascades, including beta-adrenergic receptors, in adipocytes are not greatly impaired by diabetes, and therefore, the unresponsiveness of these cells to glucagon is mostly due to a marked reduction in the number of glucagon receptors, probably as a result of a down-regulation by postprandial hyperglucagonemia.