ALTERATIONS IN LIVER, MUSCLE, AND ADIPOSE TISSUE INSULIN SENSITIVITY

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia. Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic, hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride >250mg/dl and HDL<45mg/dl; n=12), HIV-infected men without dyslipidemia (HIV w/o DL; n=12), and healthy men (n=6). Basal rates of glucose production (glucose Ra), glucose disposal (glucose Rd), and lipolysis (palmitate Ra) were similar between groups. The relative suppression of glucose Ra (63¿4%, 77¿2%, and 78¿3%; P=0.008) and palmitate Ra (49¿4%, 63¿3%, and 68¿3%; P=0.005) during low-dose insulin infusion (plasma insulin=30 ¿U/ml), and the relative stimulation of glucose Rd (214¿21%, 390¿25% and 393¿46%; P=0.001) during high-dose insulin infusion (plasma insulin=75¿U/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose Ra correlated with plasma adiponectin (r =0.44, P=0.02), and inversely with plasma interleukin-6 (r =-0.49, P<0.001). Stimulation of glucose Rd correlated directly with adiponectin (r=0.48, P<0.01) and inversely with IL-6 (r=-0.49, P=0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multi-organ insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action.