The 'insulin-resistance' of human obesity, and of the aging-rat model of human obesity, is well established. At the systemic level, this resistance is reflected in an attenuation of insulin's ability to regulate total-body glucose utilization. At the cellular level, it is characterized by a diminished stimulatory effect of insulin on glucose metabolism in both the adipose cell and the muscle cell. Only recently, however, has an understanding of the mechanism of insulin resistance at the cellular level begun to emerge with the development of new methodologies for examining each of the major steps in insulin action, namely insulin binding to its receptor, glucose transport across the plasma membrane and glucose metabolism. In addition, the development of an assay for quantifying the number of glucose-transport system in subcellular membrane fractions and demonstration that insulin stimulates glucose transport primarily through the translocation of glucose transport systems from an intracellular pool to the plasma membrane have now permitted a direct examination of the molecular mechanism of insulin-resistant glucose transport. The present communication briefly reviews the results of studies in this laboratory on the mechanism of the insulin-resistance of the isolated epididymal adipose cell in vitro with cellular enlargement in the aging-male-rat model of obesity.
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