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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\u2013labeled 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\u201379.5) and decreased plasma FFA concentration by 51.6% (42.0\u201358.9) (both, P &amp;lt; 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 \u03bcmol \u00b7 kg\u22121 \u00b7 min\u22121 [18.09\u201339.86] vs. placebo: 20.30 \u03bcmol \u00b7 kg\u22121 \u00b7 min\u22121 [13.67\u201330.13]; P &amp;lt; 0.01). Insulin increased phosphorylation of Akt Thr308 and glycogen synthase kinase-3\u03b2 Ser9, decreased phosphorylation of glycogen synthase (GS) site 3a + b, and increased GS activity (percent I-form) in skeletal muscle (P &amp;lt; 0.01). Acipimox decreased phosphorylation of GS (site 3a + b) (P &amp;lt; 0.02) and increased GS activity (P &amp;lt; 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.<\/jats:p>","DOI":"10.2337\/db07-0144","type":"journal-article","created":{"date-parts":[[2007,7,27]],"date-time":"2007-07-27T17:34:04Z","timestamp":1185557644000},"page":"2070-2077","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of Lipolysis Stimulates Peripheral Glucose Uptake but Has No Effect on Endogenous Glucose Production in HIV Lipodystrophy"],"prefix":"10.2337","volume":"56","author":[{"given":"Birgitte","family":"Lindegaard","sequence":"first","affiliation":[{"name":"Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark"},{"name":"The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Fr\u00f8sig","sequence":"additional","affiliation":[{"name":"The Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie W.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark"},{"name":"The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Plomgaard","sequence":"additional","affiliation":[{"name":"Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark"},{"name":"The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Ditlevsen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Mittendorfer","sequence":"additional","affiliation":[{"name":"School of Medicine, Washington University, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Van Hall","sequence":"additional","affiliation":[{"name":"Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark"},{"name":"The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen F.P.","family":"Wojtaszewski","sequence":"additional","affiliation":[{"name":"The Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente K.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen, Denmark"},{"name":"The Copenhagen Muscle Research Centre, Rigshospitalet Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208472647900_R1","doi-asserted-by":"crossref","unstructured":"Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, Cooper DA: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. 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