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 (i.v.) 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.(ABSTRACT TRUNCATED AT 250 WORDS)