Three levels of regulation of glucose transport in the isolated rat adipose cell can be identified. First, an acute stimulatory action of insulin increases the maximum transport velocity primarily by the translocation of glucose transporters from a large intracellular pool to the plasma membrane. Second, lipolytic hormones such as isoproterenol inhibit insulin-stimulated glucose transport. However, their action is prevented by the presence of adenosine and other antilipolytic agents, and occurs through a decrease in glucose transporter intrinsic activity. Furthermore, their action is mediated by a cAMP-independent mechanism. Third, experimental insulin-resistant metabolic states such as streptozotocin diabetes are accompanied by a markedly resistant glucose transport response to insulin which is the consequence of a chronic depletion of glucose transporters from the intracellular pool. The biochemical mechanism of insulin action on glucose transport in the rat adipose cell has been studied using a photochemical crosslinking agent to covalently bind (H3)cytochalasin B to the glucose transporter in plasma membranes and low-density microsomes from basal and insulin-stimulated cells. The results demonstrate 1) a heterogeneity of glucose transporter species in the intracellular pool while the plasma membrane transporters are more uniform in structure; 2) a differential sensitivity of the glucose transporter isoforms to neuraminidase suggesting that this heterogeneity is at lease partially due to differences in glycosylation state, and 3) an apparent translocation of the pH 5.6 glucose transporter isoform from the low-density microsomes to the plasma membrane in response to insulin, but not of the pH 6.4 isoform. In a preliminary series of experiments, insulin appears to stimulate glucose transport in isolated human adipose cells by a translocation mechanism similar to that observed in rat adipose cells and diaphragm.
