Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution

Meininger, Gary; Hadigan, Colleen; Laposata, Michael; Brown, J. Howard; Rabe, Jessica; Louca, Joseph; Aliabadi, Negar; Grinspoon, Steven

doi:10.1053/meta.2002.29999

Cited by 74 publications

(52 citation statements)

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“…This is contrasted with glucose regulation in HIVϩIGT subjects, where absolute basal glucose R a and R d (micromoles per kilogram FFM per hour) were similar among the groups, but insulin action on glucose R a and R d was blunted in HIVϩIGT subjects during insulin infusion. Taken together, these findings indicate that dysregulated fasting leucine and protein metabolism, along with impairments in glucose and fatty acid metabolism (9,11,(13)(14)(15)(16)18), may be integrated and represent metabolic syndromes associated with HIV infection and HAART.…”

Section: Discussionmentioning

confidence: 91%

“…The mechanism is multifactorial and likely comprises the effects of chronic viral infection, host response, anti-HIV medications, genetics, lifestyle/behavioral factors on intracellular signaling pathways, and substrate partitioning and sensing (9,10). Several groups have reported that HIV-associated insulin resistance is characterized by perturbations in glucose and lipid metabolism, which are common to type 2 diabetes (11)(12)(13)(14)(15)(16)(17)(18)(19). Whether HIV-associated insulin resistance is associated with defects in amino acid and protein metabolism has not been addressed.…”

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confidence: 99%

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Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

et al. 2006

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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 2 H 2 -glucose and 13 C-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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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

et al. 2006

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“…Some PIs might also cause mitochondrial toxicity [172]. Additionally, the increase in FFA levels associated with PIs, as well as with fat redistribution, might also have a role in the development of IR (see lipotoxicity) [173].…”

Section: Insulin Resistancementioning

confidence: 99%

Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome

Freitas¹,

Carvalho²,

Souto³

et al. 2013

Current Perspectives in HIV Infection

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“…IV-associated lipodystrophy (HIV lipodystrophy) is characterized by various degrees of subcutaneous fat loss, visceral fat accumulation, and metabolic disturbances, including peripheral and hepatic insulin resistance (1-3) and elevated plasma free fatty acids (FFAs) (4). Increased plasma FFA concentration is due to increased lipolysis (5,6), with increased net release of FFAs from adipose tissue (5,7).…”

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confidence: 99%

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

et al. 2007

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HIV-infected patients with lipodystrophy (HIV lipodystrophy) are insulin resistant and have elevated plasma free fatty acid (FFA) concentrations. We aimed to explore the mechanisms underlying FFA-induced insulin resistance in patients with HIV lipodystrophy. Using a randomized, placebo-controlled, cross-over design, we studied the effects of an overnight acipimox-induced suppression of FFAs on glucose and FFA metabolism by using stable isotopelabeled tracer techniques during basal conditions and a two-stage euglycemic-hyperinsulinemic clamp (20 and 50 mU insulin/m 2 per min, respectively) in nine patients with nondiabetic HIV lipodystrophy. All patients received antiretroviral therapy. Biopsies from the vastus lateralis muscle were obtained during each stage of the clamp. Acipimox treatment reduced basal FFA rate of appearance by 68.9% (95% CI 52.6 -79.5) and decreased plasma FFA concentration by 51.6% (42.0 -58.9) (both, P < 0.0001). Endogenous glucose production was not influenced by acipimox. During the clamp, the increase in glucose uptake was significantly greater after acipimox treatment compared with placebo (acipimox: 26. 85 , decreased phosphorylation of glycogen synthase (GS) site 3a ؉ b, and increased GS activity (percent I-form) in skeletal muscle (P < 0.01). Acipimox decreased phosphorylation of GS (site 3a ؉ b) (P < 0.02) and increased GS activity (P < 0.01) in muscle. The present study provides direct evidence that suppression of lipolysis in patients with HIV lipodystrophy improves insulin-stimulated peripheral glucose uptake. The increased glucose uptake may in part be explained by increased dephosphorylation of GS (site 3a ؉ b), resulting in increased GS activity.

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Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution

Cited by 74 publications

References 0 publications

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome

Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy

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