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: 7721456
• 负责人: Dominic N Reeds
• 金额: $ 0.61万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721456
• 关键词: Adipose tissue; Computer Retrieval of Information on Scientific Projects Database; Dose; Dyslipidemias; Funding; Glucose; Grant; HIV; HIV Infections; Infusion procedures; Institution; Insulin; Insulin Resistance; Interleukin-6; Label; Lipolysis; Liver; Muscle; N(delta)-acetylornithine, -isomer; N-dodecanoylglutamic acid, -isomer, sodium salt; Organ; Palmitates; Pathogenesis; Patients; Plasma; Rate; Relative (related person); Research; Research Personnel; Resources; Skeletal Muscle; Source; Staging; Tracer; Triglycerides; United States National Institutes of Health; adipokines; adiponectin; alpha-difluoromethyl-DOPA, -isomer; alpha-methylornithine dihydrochloride, -isomer; glucose disposal; glucose production; healthy volunteer; insulin sensitivity; men

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 HIV感染和血脂异常男性患者肝脏、肌肉和脂肪组织胰岛素敏感性的改变。在HIV感染的患者中，血脂异常很常见。在这项研究中，使用两级正血糖、高胰岛素钳夹，并注入稳定的同位素标记示踪剂，评估了患有人类免疫缺陷病毒(HIV-DL；血浆甘油三酯250 mg/dl和高密度脂蛋白45 mg/dl；n=12)的HIV感染男性(HIV w/o Dl；n=12)和健康男性(n=6)骨骼肌、肝脏和脂肪组织中的胰岛素作用。两组间葡萄糖产生(葡萄糖Ra)、葡萄糖处置(葡萄糖Rd)和脂解(棕榈酸酯Ra)的基础速率相似。低剂量胰岛素输注(血浆胰岛素=30U/ml)时葡萄糖Ra相对抑制率(63.4%、77.2%和78.3%；P=0.008)和棕榈酸酯Ra相对抑制率(49.4%、63.3%和68.3%；P=0.005)和大剂量胰岛素输注(血浆胰岛素=75U/ml)时葡萄糖Rd的相对刺激率(214.21%、39025%和393±46%；P=0.001)分别低于HIVW/O组和健康志愿者。基础血糖Ra降低与血浆脂联素水平呈正相关(r=0.44，P=0.02)，与白介素6水平呈负相关(r=-0.49，P<0.001)。糖负荷与脂联素呈正相关(r=0.48，P&lt；0.01)，与IL-6呈负相关(r=-0.49，P=0.02)。我们的结论是，HIV感染者的血脂异常是多器官胰岛素抵抗的标志，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。