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.

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