Differential tissue sensitivity to elevated endogenous insulin levels during experimental peritonitis in rats

Abstract

Disturbances of glucose metabolism consequent to experimental peritonitis in rats were studied by measurement of insulin-related metabolism of isolated tissues in correlation with blood insulin and substrate levels. Blood insulin concentrations were threefold higher in infected fasting rats than in normal fasting controls, despite approximately equal blood glucose concentrations, suggesting resistance to the hypoglycemic action of insulin. The increased circulating insulin was associated with a threefold elevation of the insulin-sensitive adipose tissue pyruvate dehydrogenase enzyme complex, and a threefold increase in the rate of conversion of glucose to CO 2 by fragments of epididymal fat pads. Fasting infected animals also had reduced circulating nonesterified fatty acids and relatively less depletion of epididymal adipose tissue, when compared to fasted controls presumably due to the potent action of insulin in opposing lipid mobilization. In contrast, diaphragm pyruvate dehydrogenase was not elevated, nor was diaphragm glucose conversion to CO 2 stimulated in response to the elevated circulating insulin. It is proposed that reduced fat mobilization without concomitantly accelerated glucose oxidation by muscle may result in insufficient metabolic fuel for muscle and this may, in turn, promote amino acid combustion by muscle to meet cellular energy requirements. This suggested mechanism may provide a hypothetical biochemical explanation for the excessive protein catabolism associated with severe infection.