HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db07-0144v1 56/8/2070    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lindegaard, B. Articles by Pedersen, B. K. Search for Related Content PubMed PubMed Citation Articles by Lindegaard, B. Articles by Pedersen, B. K. Social Bookmarking                What's this?

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

¹ Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark
² The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark
³ The Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
⁴ Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
⁵ School of Medicine, Washington University, St. Louis, Missouri

Address correspondence and reprint requests to Birgitte Lindegaard, Centre of Inflammation and Metabolism at the Department of Infectious Diseases M7641, Rigshospitalet, Blegdamvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: blm{at}rh.dk

Abbreviations: ARV, antiretroviral; FFA, free fatty acid; G6P, glucose-6-phosphate; GS, glycogen synthase; GSK, glycogen synthase kinase; IRS, insulin receptor substrate

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 isotope–labeled tracer techniques during basal conditions and a two-stage euglycemic-hyperinsulinemic clamp (20 and 50 mU insulin/m² 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 µmol · kg^–1 · min^–1 [18.09–39.86] vs. placebo: 20.30 µmol · kg^–1 · min^–1 [13.67–30.13]; P < 0.01). Insulin increased phosphorylation of Akt Thr³⁰⁸ and glycogen synthase kinase-3ß Ser⁹, 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?