Modulation of glucose transport in hamster adipocytes by insulin and byβ- andα2-adrenoceptor agonists

Glucose transport in hamster adipocytes and its modulation by insulin and isoprenaline was characterized with the aid of the non-metabolizable hexose 3-0-methylglucose. Insulin stimulated the initial uptake rates by an increase in Vmax of the transport without any detectable change in Km. The hormone concentration producing half maximal stimulation was identical to that required in rat adipocytes. However, hamster adipocytes were much less responsive to insulin (3-fold stimulation as compared to a 12-fold stimulation in rat fat cells), and maximal transport rates were 10-fold lower than that observed in rat adipocytes. Accordingly, the number of glucose transporters, as assessed by glucose-inhibitable cytochalasin-B binding, was considerably lower in plasma membranes of hamster adipocytes. Moreover, no transporters were detected in the low-density microsomes which in insulin-sensitive cell types represent the intracellular pool of recruitable glucose transporters. The relative insulin resistance of the hamster fat cells may therefore be due to a depleted pool of intracellular glucose transporters. In the presence of adenosine, theβ-adrenoceptor agonist isoprenaline produced a moderate stimulation of the basal transport rate which was antagonized by theα2-agonist clonidine. If adenosine deaminase was added in order to remove endogenous adenosine, isoprenaline inhibited the insulin-stimulated transport by 50%. In contrast to the stimulatory effects of insulin and isoproterenol, the inhibitory effect of the catecholamine was reversed by cooling the cells to 22°. Glucagon produced a comparable inhibition, suggesting that the inhibitory effect was mediated by adenylate cyclase or its regulatory subunits. Theα2-adrenoceptor agonist clonidine fully antagonized the inhibitory effect of isoproterenol. The effect of glucagon was reversed by adrenaline, if propranolol was added in order to unmask the α2-agonist action of the catecholamine. The data demonstrate thatα2-adrenoceptors participate in the regulation of glucose transport by antagonizing both theβ-receptor mediated stimulation and inhibition produced by catecholamines.