ALTERATIONS IN LIVER, MUSCLE, AND ADIPOSE TISSUE INSULIN SENSITIVITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。男性HIV感染和血脂异常患者肝脏、肌肉和脂肪组织胰岛素敏感性的改变：血脂异常在HIV感染患者中很常见。在本研究中，采用两阶段升糖、高胰岛素钳，输注稳定同位素标记的示踪剂，评估了患有血脂异常的HIV感染者（HIV- dl；血浆甘油三酯>250mg/dl和HDL<45mg/dl; n=12）、无血脂异常的HIV感染者（HIV w/o dl; n=12）和健康男性（n=6）的骨骼肌、肝脏和脂肪组织中胰岛素的作用。葡萄糖生成（葡萄糖Ra）、葡萄糖处理（葡萄糖Rd）和脂肪分解（棕榈酸酯Ra）的基础速率在两组之间相似。低剂量胰岛素输注（血浆胰岛素=30¿U/ml）时，HIV-DL患者的葡萄糖Ra（63¿4%,77¿2%,78¿3%，P=0.008）和棕榈酸Ra（49¿4%,63¿3%,68¿3%，P=0.005）的相对抑制和高剂量胰岛素输注（血浆胰岛素=75¿U/ml）时葡萄糖Rd（214¿21%,390¿25%,393¿46%，P=0.001）的相对刺激分别低于HIV /o DL和健康志愿者。基础葡萄糖Ra的抑制与血浆脂联素相关（r =0.44， P=0.02），与血浆白细胞介素-6呈负相关（r =-0.49， P<0.001）。葡萄糖Rd刺激与脂联素呈正相关（r=0.48， P<0.01），与IL-6呈负相关（r=-0.49， P=0.02）。我们得出结论，hiv感染男性的血脂异常是多器官胰岛素抵抗的指示，循环脂肪因子可能在胰岛素作用受损的发病机制中起重要作用。

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.