title: Effects of systemic infusions of endotoxin, tumor necrosis factor, and interleukin-1 on glucose metabolism in the rat: relationship to endogenous glucose production and peripheral tissue glucose uptake.
abstract: This study was performed to characterize and compare the actions of insulin on hepatic glucose production and peripheral glucose utilization during infusions of endotoxin, tumor necrosis factor (TNF), interleukin-1 (IL-1), and a combination of IL-1 and TNF in the rat. The euglycemic hyperinsulinemic clamp technique was combined with a primed-constant tracer infusion of high-performance liquid chromatography (HPLC)-purified 3H-3-glucose for estimation of whole-body glucose appearance and utilization rates; 14C-deoxyglucose (14C-DG) uptake was also measured in specific tissues following intravenous bolus administration. As expected, acute endotoxemia resulted in a significant reduction of glucose infusion during the clamp procedure (insulin concentration, 100 microU/mL), suggesting decreased insulin action. Similarly, infusion of TNF decreased the rate of glucose infusion necessary to maintain euglycemia. However, differences between endotoxin- and cytokine-treated rats were noted in whole-body glucose appearance (or disappearance) rates. Whereas endotoxin infusion predominantly decreased whole-body glucose uptake, suggesting diminished utilization in skeletal muscles, cytokine infusions were associated with a measurable hepatic glucose output despite hyperinsulinemia. In contrast, both cytokine and endotoxin administration decreased the rate of 14C-DG uptake by muscle tissue. These results demonstrate that TNF, IL-1, and endotoxin can induce a state of insulin resistance when infused continuously; the results also emphasize the complexity of regulation of glucose homeostasis during infection and sepsis.
authors.affiliation: Laboratory of Nutrition/Infection, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
authors.forename: P R
authors.initials: PR
authors.lastname: Ling
authors.forename: B R
authors.initials: BR
authors.lastname: Bistrian
authors.forename: B
authors.initials: B
authors.lastname: Mendez
authors.forename: N W
authors.initials: NW
authors.lastname: Istfan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003847:Deoxyglucose / Q000008:administration & dosage; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004731:Endotoxins; D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D003847:Deoxyglucose; D005947:Glucose