The influence of acute physiological increments of cortisol on fuel metabolism and insulin binding to monocytes in normal humans

The role of physiological hypercortisolemia in the regulation of fuel metabolism in man was examined during a 5-h primed-continuous infusion of cortisol which raised plasma cortisol levels to 40 μg/dl. Plasma glucose increased by 15-20 mg/dl (P < 0.005) in spite of unchanged rates of glucose production. Glucose uptake and clearance, on the other hand, fell by 15% (P < 0.05) and 30% (P < 0.005), respectively, thereby accounting for cortisol-induced hyperglycemia. Total blood ketones during cortisol infusion increased 3-fold above saline control values (P < 0.01) despite comparable FFA levels in the two groups. In addition, there was a selective 40% rise in total branched chain amino acids (P < 0.005) during cortisol infusion. These effects of cortisol on glucose, ketone, and amino acid metabolism occurred in the absence of significant changes in the plasma insulin or glucagon concentration. Furthermore, cortisol infusion had no effect on [¹²⁵I]insulin binding to circulating monocytes. Our data thus suggest that acute elevations of plasma cortisol have antiinsulin effects in man which may occur independent of alterations in insulin receptors.