Insulin resistance and substrate utilization in human endotoxemia.

Infection results in a state of insulin resistance, but the pathogenesis is poorly understood. Intravenous administration of bacterial lipopolysaccharide (LPS) has been used to mimic the febrile and systemic inflammatory responses to infection, but it is unclear whether LPS induces insulin resistance in man. To investigate the effects of LPS on insulin sensitivity and substrate utilization, we administered, in paired cross-over studies, either 20 U/kg Escherichia coli endotoxin or saline control to healthy volunteers (n = 6) 120 min after the start of a 10-h euglycemic hyperinsulinemic clamp (insulin infusion rate, 80 mU/m2·min). LPS induced a fever, tachycardia, and mild arterial hypotension. Glucose utilization increased abruptly 120 min after LPS administration (+64.1 ± 12.0%; P< 0.003), but then declined progressively, and insulin resistance was evident by 420 min (+1.9 ± 3.5%; P < 0.05). The reduction in glucose utilization, like that observed in sepsis, was related to impaired nonoxidative glucose d...