ALTERATIONS IN LIVER, MUSCLE, AND ADIPOSE TISSUE INSULIN SENSITIVITY

肝脏、肌肉和脂肪组织胰岛素敏感性的改变

• 批准号: 7355257
• 负责人: Dominic N Reeds
• 金额: $ 1.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355257
• 关键词: ALTERATIONS; LIVER; MUSCLE; ADIPOSE; TISSUE

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。HIV感染和血脂异常男性的肝脏、肌肉和脂肪组织胰岛素敏感性改变：血脂异常在HIV感染患者中很常见。在这项研究中，使用两阶段正常血糖、高胰岛素钳夹，并输注稳定的同位素标记示踪剂，来评估患有血脂异常的HIV感染男性（HIV-DL;血浆甘油三酯> 250 mg/dl和HDL<45 mg/dl; n=12）、没有血脂异常的HIV感染男性（HIV w/o DL; n =12）和健康男性（n=6）的骨骼肌、肝脏和脂肪组织中的胰岛素作用。两组之间的基础葡萄糖生成率（葡萄糖Ra）、葡萄糖处置率（葡萄糖Rd）和脂解率（棕榈酸Ra）相似。葡萄糖Ra的相对抑制（63 <$4%、77 <$2%和78 <$3%; P=0.008）和棕榈酸Ra（49 <$4%、63 <$3%和68 <$3%; P=0.005）（血浆胰岛素=30 <$U/ml），以及葡萄糖Rd的相对刺激（214 <$21%、390 <$25%和393 <$46%; P=0.001）（血浆胰岛素=75 μ U/ml）分别低于HIV w/o DL和健康志愿者。基础血糖Ra的降低与血浆脂联素水平呈正相关（r =0.44，P=0.02），与血浆白细胞介素6水平呈负相关（r =-0.49，P<0.001）。葡萄糖刺激Rd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）。我们的结论是，HIV感染的男性血脂异常是多器官胰岛素抵抗的指标，循环脂肪因子可能是重要的胰岛素作用受损的发病机制。