Effects of Experimental Insulin‐Dependent Diabetes on the β‐Adrenergic‐Receptor‐Coupled Adenylate‐Cyclase System and Lipolysis in Fat Cells of the Rat

According to the hypothesis put forward by Zumstein et al. [ Eur. J. Biochem. , (1980) 105 , 187–194], we have investigated whether the increased sensitivity of adenylate cyclase to catecholamines they observed in streptozotocintreated rat adipocytes could be due to altered β‐adrenergic receptor number, affinity or coupling to adenylate cyclase. The present report shows the following in streptozotocin‐treated rat adipocytes.1 A 60–70% decrease in the number of β‐adrenergic receptors and in basal and isoproterenol maximally‐stimulated adenylate cyclase activities, a 45% decrease in the 5′‐nucleotidase activity and a 60% reduction in membrane protein content per cell. 2 An almost complete reversion of these alterations by insulin‐treatment. 3 An unaltered β‐adrenergic‐receptor affinity towards β‐agonists and antagonists, an unaltered sensitivity of adenylate cyclase to guanine nucleotides and to isoproterenol (in the presence of guanine nucleotides) and an unaltered adenylate cyclase responsiveness (expressed as the percentage of basal activity) to isoproterenol and guanine nucleotides. 4 A 60–70% reduction of the basal lipolytic activities per cell and those stimulated by isoproterenol, adrenocorticotropin and dibutyryladenosine 3′,5′‐monophosphate, but no modification of either the sensitivity or the responsiveness (expressed as the percentage of basal activity) of lipolysis to these effectors.From this study, it can be concluded that in streptozotocin‐treated rat adipocytes, the sensitivity of the β‐receptor‐coupled adenylate cyclase system to catecholamines is unimpaired, but the number of β‐receptors and of adenylate cyclase catalytic‐subunits per adipocyte are reduced, an effect which seems related to defective protein biosynthesis induced by insulin deficiency.