The Effects Of Tumor Necrosis Factor-Alpha On Insulin Sensitivity And Glucose-Lipid Metabolism In Mice

Objective To establish Euglycemic-hyperinsulinemic clamp technology and investigate the effects of tumor necrosis factor-alpha (TNF-α) on insulin sensitivity and glucose-lipid metabolism in mice.Methods Male C57BL/6J mice were randomly divided into 4 groups. The mice were given an intraperitoneal injection of TNF-α(H group,6μg/kg;M group,3μg/kg and L group,1μg/kg) and saline ( NC group) for 7 days. The insulin sensitivity and glucose lipid metabolism in awake mice were evaluated by intravenous glucose tolerance test (IVGTT) and hyperinsulinemic-euglycemic clamp technique combined with 3-[3H] glucose as a tracer.Results In basal, fasting blood glucose ( FBG ), plasma insulin ( Fins ) and plasma free fatty acids (FFA) were elevated significantly in H group compared with NC and L groups and the elevations were related to the dosage of TNF-α(P<0.01 and P<0.05). After glucose stimulation blood glucose and insulin levels were elevated immediately, and the extents of elevation were higher in H group than NC and L group (P<0.01 and P<0.05).In basal-state, the glucose rate of disappearance (GRd) in H group were increased significantly compared to NC group (P<0.01). During the clamp, there were a significant increase in insulin level and significant decrease in glucose infusion rate (GIR) and GRd in H group compared to NC group (P<0.01 and P<0.05).The suppressive effects of insulin on hepatic glucose production (HGP) and lipolysis were significantly blunted in H group.Conclusion TNF-αtreatment induced insulin resistance by elevating fasting blood glucose, plasma insulin and FFA levels and blunting the suppressive effects of insulin on HGP and lipolysis in mice.