Whole body proteolysis rate is elevated in HIV-associated insulin resistance

摘要

Type 2 diabetes (T2DM) 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 people 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+ with normal glucose tolerance, and 21 HIV+IGT. 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 IL-8 and FFA levels, and higher lipid oxidation rates during the clamp than the other two groups. The findings implicate several factors in the insulin-signaling pathway that 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.