In vivo skeletal muscle insulin resistance during E coli endotoxin shock in the dog

The ability of insulin to promote glucose diffusion into skeletal muscle before and during gram-negative endotoxin shock was studied in mongrel dogs anesthetized with sodium pentobarbital. The in vivo, isolated, innervated, constant-flow-perfused gracilis muscle preparation was used. Prior to shock induction, close intraarterial insulin infusion resulted in a 320% increase in muscle glucose uptake. However, at one, two, and three hours of endotoxin shock, gracilis muscle glucose uptake was unaltered by insulin infusion. This loss of responsiveness to insulin occurred with no alteration in gracilis muscle oxygen uptake, muscle venous PO2, or muscle blood flow. During control experiments, however, the muscle response to intraarterial infusion of insulin (increased glucose uptake) was unaltered during the three-hour control period. These data demonstrate that skeletal muscle insulin resistance develops early and is maintained during three hours of endotoxin shock in the dog.