Gram-negative infection increases noninsulin-mediated glucose disposal

Abstract

Peripheral glucose uptake can occur by either insulin- or noninsulin-mediated mechanisms, and the two pathways appear to be regulated independently. Using the euglycemic hyperinsulinemic clamp technique, we have previously demonstrated that sepsis induces whole body insulin resistance. The purpose of the present study was to determine whether infection also alters noninsulin-mediated glucose uptake (NIMGU) and, if so, which tissues are affected. Studies were performed in chronically catheterized conscious rats under either basal (6 mM glucose, 30 microU/ml insulin) or insulinopenic conditions to determine NIMGU. Hypermetabolic sepsis was induced by sc injections of live Escherichia coli, and 24 h later a tracer amount of [U-14C]deoxy-2-glucose was injected for the determination of the in vivo glucose metabolic rate (Rg) in selected tissues. Our results indicate that NIMGU is the predominant route of glucose disposal in both septic and nonseptic rats, accounting for 79-83% of the total rate of glucose disposal. Because the rate of whole body glucose disposal was increased by sepsis, the absolute rate of NIMGU was 46% higher in septic rats than in nonseptic animals. This increase was the result of the elevated Rg in liver, spleen, ileum, and lung. Sepsis also increased whole body insulin-mediated glucose uptake by 88% under basal conditions, and this was due to an enhanced glucose uptake by muscle and skin. In insulinopenic animals in which the plasma glucose concentration was elevated to 17 mM, whole body glucose disposal increased by 107% in nonseptic animals, but by only 32% in septic rats. The hyperglycemic-induced increment in organ Rg was smaller in all tissues examined from septic animals. However, the absolute rate of whole body and tissue glucose utilization was not different between the two groups. These results indicate that gram-negative infection increases whole body NIMGU, which results from an enhanced rate of glucose utilization by tissues rich in mononuclear phagocytes, including the liver, spleen, ileum, and lung, but not by muscle.