WHOLE-BODY PROTEOLYSIS RATE IS ELEVATED IN HIV-ASSOCIATED INSULIN RESISTANCE

HIV 相关的胰岛素抵抗导致全身蛋白水解率升高

• 批准号: 7721508
• 负责人: Dominic N Reeds
• 金额: $ 0.48万
• 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/7721508
• 关键词: Amino Acids; Appearance; Computer Retrieval of Information on Scientific Projects Database; Condition; Fasting; Funding; Gluconeogenesis; Glucose; Grant; HIV; Hyperglycemia; Hyperinsulinism; Individual; Infusion procedures; Institution; Insulin; Insulin Resistance; Insulin Signaling Pathway; Interleukin-8; Kinetics; Leucine; Lipids; Measures; Metabolism; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Plasma; Proteolysis; Rate; Research; Research Personnel; Resources; Serum; Source; United States National Institutes of Health; Visceral; glucose disposal; glucose metabolism; glucose tolerance; impaired glucose tolerance; oxidation; protein metabolism; response

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. Type 2 diabetes is characterized by impaired glucose tolerance (IGT) and insulin resistance with respect to glucose metabolism but not amino acid metabolism. We examined whether whole-body leucine and protein metabolism are dysregulated in HIV-infected individuals with IGT. Glucose and leucine kinetics were measured under fasting insulin conditions and during euglycemic hyperinsulinemia using primed-constant infusions of 2H2-glucose and 13C-leucine in 10 HIV-seronegative control subjects, 16 HIV+ subjects with normal glucose tolerance, and 21 HIV+IGT subjects. Glucose disposal rate during hyperinsulinemia was lower in HIV+IGT than the other two groups. Absolute plasma leucine levels and rate of appearance (whole-body proteolysis) were higher in HIV+IGT at all insulin levels but declined in response to hyperinsulinemia in parallel to those in the other two groups. HIV+IGT had greater visceral adiposity, fasting serum interleukin (IL)-8 and free fatty acid levels, and higher lipid oxidation rates during the clamp than the other two groups. These findings implicate several factors in the insulin signaling pathway, which may be further dysregulated in HIV+IGT, and support the notion that insulin signaling pathways for glucose and leucine metabolism may be disrupted by increased proinflammatory adipocytokines (IL-8) and increased lipid oxidation. Increased proteolysis may provide amino acids for gluconeogenesis, exacerbating hyperglycemia in HIV.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 2 型糖尿病的特点是糖耐量受损 (IGT) 和与葡萄糖代谢有关的胰岛素抵抗，但与氨基酸代谢无关。我们检查了患有 IGT 的 HIV 感染者全身亮氨酸和蛋白质代谢是否失调。在 10 名 HIV 血清阴性对照受试者、16 名糖耐量正常的 HIV+ 受试者和 21 名 HIV+IGT 受试者中，使用持续灌注的 2H2-葡萄糖和 13C-亮氨酸，在空腹胰岛素条件下和正常血糖高胰岛素血症期间测量葡萄糖和亮氨酸动力学。 HIV+IGT组高胰岛素血症期间的葡萄糖处理率低于其他两组。在所有胰岛素水平下，HIV+IGT 患者的绝对血浆亮氨酸水平和出现率（全身蛋白水解）均较高，但与其他两组相比，其对高胰岛素血症的反应有所下降。与其他两组相比，HIV+IGT 组的内脏脂肪、空腹血清白细胞介素 (IL)-8 和游离脂肪酸水平更高，钳夹期间脂质氧化率更高。这些发现暗示了胰岛素信号通路中的几个因素，这些因素可能在 HIV+IGT 中进一步失调，并支持这样的观点：促炎性脂肪细胞因子 (IL-8) 增加和脂质氧化增加可能会破坏葡萄糖和亮氨酸代谢的胰岛素信号通路。蛋白水解作用的增加可能为糖异生提供氨基酸，从而加剧 HIV 患者的高血糖症。