SEPSIS-INDUCED INSULIN RESISTANCE IN RATS IS MEDIATED BY A BETA-ADRENERGIC MECHANISM

Bacterial infection decreases insulin-mediated glucose uptake (IMGU) by skeletal muscle and produces whole body insulin resistance. Because circulating catecholamines are elevated by the septic insult, the present study was performed to determine the potential role of the beta-adrenergic system in eliciting these changes. Before induction of sepsis, an infusion containing saline, propranolol, or atenolol was started and continued throughout the experimental protocol. Sepsis increased the basal rate of glucose production and utilization and impaired IMGU by peripheral tissues. The peripheral insulin resistance in septic rats was manifested by an increase in the dose producing 50% of maximal response and a decrease in the maximal responsiveness. Infusion of propranolol, a nonselective beta-adrenergic antagonist, attenuated the sepsis-induced increase in basal glucose turnover by 70% and completely prevented the decrease in IMGU by the whole body. In contrast, atenolol, a selective beta1-antagonist, did not alter the glucose metabolic response to infection. Under basal conditions, propranolol prevented or attenuated the increase in glucose uptake by the gastrocnemius, diaphragm, skin, liver, lung, spleen, and ileum normally observed in septic rats. In addition, propranolol prevented the decrease in IMGU by various muscles and skin in septic animals. These results suggest that adrenergic stimulation, probably mediated by a beta2-adrenergic mechanism, is partially responsible for the sepsis-induced increases in basal whole body glucose turnover and plays a prominent role in the development of peripheral insulin resistance in this condition.