BACKGROUND: Hyperglycemia associated with insulin resistance is common among critically ill patients. Interleukin (IL)-18 has been linked with hyperglycemia and insulin resistance in chronic disease, but the relation between IL-18 and insulin resistance during critical illness was unexplored. This study investigated whether IL-18 modulates hyperglycemia and insulin resistance during acute inflammation. METHODS: We injected lipopolysaccharide (LPS) 40 mg/kg into wild-type (WT) and IL-18 knockout (KO) mice to induce endotoxemia and examined insulin resistance and insulin-dependent signaling pathways during the acute phase. RESULTS: During the first hour after LPS treatment, IL-18 KO mice showed higher blood glucose and insulin and less insulin receptor substrate-1 and less phosphorylated Akt in the liver compared with WT mice. Interleukin-18 KO mice exhibited better survival after LPS treatment. CONCLUSIONS: The findings suggest that endogenous IL-18 may attenuate hyperglycemia and modulate insulin signaling in liver. Accordingly, IL-18 may modulate glucose tolerance during acute inflammation.
BACKGROUND:Hyperglycemia associated with insulin resistance is common among critically ill patients. Interleukin (IL)-18 has been linked with hyperglycemia and insulin resistance in chronic disease, but the relation between IL-18 and insulin resistance during critical illness was unexplored. This study investigated whether IL-18 modulates hyperglycemia and insulin resistance during acute inflammation. METHODS: We injected lipopolysaccharide (LPS) 40 mg/kg into wild-type (WT) and IL-18 knockout (KO) mice to induce endotoxemia and examined insulin resistance and insulin-dependent signaling pathways during the acute phase. RESULTS: During the first hour after LPS treatment, IL-18 KO mice showed higher blood glucose and insulin and less insulin receptor substrate-1 and less phosphorylated Akt in the liver compared with WT mice. Interleukin-18 KO mice exhibited better survival after LPS treatment. CONCLUSIONS: The findings suggest that endogenous IL-18 may attenuate hyperglycemia and modulate insulin signaling in liver. Accordingly, IL-18 may modulate glucose tolerance during acute inflammation.
Authors: G van den Berghe; P Wouters; F Weekers; C Verwaest; F Bruyninckx; M Schetz; D Vlasselaers; P Ferdinande; P Lauwers; R Bouillon Journal: N Engl J Med Date: 2001-11-08 Impact factor: 91.245
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Authors: Mihai G Netea; Leo A B Joosten; Eli Lewis; Dalan R Jensen; Peter J Voshol; Bart Jan Kullberg; Cees J Tack; Han van Krieken; Soo-Hyun Kim; Anton F Stalenhoef; Fons A van de Loo; Ineke Verschueren; Leslie Pulawa; Shizuo Akira; Robert H Eckel; Charles A Dinarello; Wim van den Berg; Jos W M van der Meer Journal: Nat Med Date: 2006-05-28 Impact factor: 53.440