Insulin-like action of E. coli endotoxin in promoting skeletal muscle glucose uptake in the dog.

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. The effects of infusion of small amounts of E. coli endotoxin into the artery of isolated, innervated, constant-flow-perfused gracilis muscles on glucose uptake and other metabolic variables were determined. Locally infused endotoxin consistently caused a significant and substantial increase in skeletal muscle glucose uptake with no alterations in muscle arterio-venous difference of insulin, oxygen, carbon dioxide, or pH, or in venous blood hematocrit or temperature. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. On the other hand, when endotoxin was given systemically to induce shock, gracilis muscle glucose uptake was maintained for the duration of the 6-hr experiment. These differences we feel reflect the reduction in plasma endotoxin concentration mediated by the reticuloendothelial system (RES). On the other hand, live E. coli septic shock was associated with an increase in glucose uptake in the constant-flow-perfused gracilis muscle after 4.5 hr of shock. We believe this increase in muscle glucose uptake resulted from the direct effects of endotoxin, whose plasma concentration presumably increases substantially as the RES is overwhelmed and becomes less effective. The contribution of this phenomenon to the progressive hypoglycemia characteristic of gram-negative endotoxin or septic shock cannot be evaluated from this study, although it is probably substantial.