TY - JOUR
T1 - Whole-body proteolysis rate is elevated in HIV-associated insulin resistance
AU - Reeds, Dominic N.
AU - Cade, W. Todd
AU - Patterson, Bruce W.
AU - Powderly, William G.
AU - Klein, Samuel
AU - Yarasheski, Kevin E.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - 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 2H 2-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.
AB - 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 2H 2-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.
UR - http://www.scopus.com/inward/record.url?scp=33750874065&partnerID=8YFLogxK
U2 - 10.2337/db06-0255
DO - 10.2337/db06-0255
M3 - Article
C2 - 17003352
AN - SCOPUS:33750874065
VL - 55
SP - 2849
EP - 2855
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -