EFFECT OF HIGH-DOSE ENDOTOXIN ON GLUCOSE-PRODUCTION AND UTILIZATION

The purpose of the present study was to determine how a high dose of endotoxin (lipopolysaccharide [LPS]), which produces hypoglycemia, alters in vivo glucose uptake by individual tissues. Catheterized conscious fasted rats were injected intravenously (IV) with either saline, LPS ( 1 mg 100 g body weight [BW], lethal dose [LD] 100), or 3-mercaptopicolinic acid (3-MP), an inhibitor of gluconeogenesis. In the latter two groups, blood glucose levels were clamped at either 6 mmol/L (euglycemia) or 3 mmol/L (hypoglycemia). In the first series of experiments, whole-body glucose flux was determined using [3-3H]glucose, and in the second study in vivo glucose uptake (Rg) by individual tissues was estimated by the tracer [U-14C]-2-deoxyglucose technique. The relative contribution of hypoglycemia per se to the LPS effect was determined by comparing the values from LPS- versus 3-MP-treated animals. There was no difference in the rate of whole-body glucose utilization (Rd) between saline-infused control rats and LPS-treated animals that were hypoglycemic. However, Rg by diaphragm, spleen, liver, and lung was increased in hypoglycemic LPS-treated rats. The increased Rg in these tissues was not observed in 3-MP-treated rats with a comparable hypoglycemia. Only the gastrocnemius muscle showed a reduction in Rg under hypoglycemic conditions, and the decrease was similar in both LPS- and 3-MP-treated animals. When sufficient glucose was infused into LPS-injected rats to maintain euglycemia, whole-body glucose Rd was increased compared with that in hypoglycemic LPS-treated rats. This increase resulted from a normalization of Rg by skeletal muscle as well as an enhanced Rg by diaphragm, spleen, ileum, skin, kidney, and fat. These data indicate that the hypoglycemia produced by high-dose LPS resulted from both an impairment in glucose production and a relative stimulation of glucose disposal by selective tissues. The enhanced Rg by diaphragm, spleen, liver, and lung in LPS-treated rats is masked by the reduction in Rg by skeletal muscle. Although the decreased Rg by gastrocnemius muscle appeared to result from a decrease in blood glucose and/or insulin levels, the enhanced uptake of glucose by other tissues after LPS must have occurred predominantly via a non-insulin-mediated mechanism. © 1993.