{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:59:34Z","timestamp":1761512374373},"reference-count":52,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:p>More than 40% of HIV-infected patients on highly active antiretroviral therapy (HAART) experience fat redistribution (lipodystrophy), a syndrome associated with insulin resistance primarily affecting insulin-stimulated nonoxidative glucose metabolism (NOGMins). Skeletal muscle biopsies, obtained from 18 lipodystrophic nondiabetic patients (LIPO) and 18 nondiabetic patients without lipodystrophy (NONLIPO) before and during hyperinsulinemic (40 mU \u00b7 m\u22122 \u00b7 min\u22121)-euglycemic clamps, were analyzed for insulin signaling effectors. All patients were on HAART. Both LIPO and NONLIPO patients were normoglycemic (4.9 \u00b1 0.1 and 4.8 \u00b1 0.1 mmol\/l, respectively); however, NOGMins was reduced by 49% in LIPO patients (P &amp;lt; 0.001). NOGMins correlated positively with insulin-stimulated glycogen synthase activity (I-form, P &amp;lt; 0.001, n = 36). Glycogen synthase activity (I-form) correlated inversely with phosphorylation of glycogen synthase sites 2+2a (P &amp;lt; 0.001, n = 36) and sites 3a+b (P &amp;lt; 0.001, n = 36) during clamp. Incremental glycogen synthase-kinase\u20133\u03b1 and \u20133\u03b2 phosphorylation was attenuated in LIPO patients (Ps &amp;lt; 0.05). Insulin-stimulated Akt Ser473 and Akt Thr308 phosphorylation was decreased in LIPO patients (P &amp;lt; 0.05), whereas insulin receptor substrate-1\u2013associated phosphatidylinositol (PI) 3-kinase activity increased significantly (P &amp;lt; 0.001) and similarly (NS) in both groups during clamp. Thus, low glycogen synthase activity explained impaired NOGMins in HIV lipodystrophy, and insulin signaling defects were downstream of PI 3-kinase at the level of Akt. These results suggest mechanisms for the insulin resistance greatly enhancing the risk of type 2 diabetes in HIV lipodystrophy.<\/jats:p>","DOI":"10.2337\/diabetes.54.12.3474","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"3474-3483","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":27,"title":["Skeletal Muscle Insulin Signaling Defects Downstream of Phosphatidylinositol 3-Kinase at the Level of Akt Are Associated With Impaired Nonoxidative Glucose Disposal in HIV Lipodystrophy"],"prefix":"10.2337","volume":"54","author":[{"given":"Steen B.","family":"Haugaard","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen"},{"name":"Department of Endocrinology and Internal Medicine, Hvidovre University Hospital, Hvidovre, Copenhagen"},{"name":"Clinical Research Unit, Hvidovre University Hospital, Hvidovre, Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ove","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen"},{"name":"Clinical Research Unit, Hvidovre University Hospital, Hvidovre, Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sten","family":"Madsbad","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Hvidovre University Hospital, Hvidovre, Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Fr\u00f8sig","sequence":"additional","affiliation":[{"name":"Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Department of Human Physiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens Ole","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen F.P.","family":"Wojtaszewski","sequence":"additional","affiliation":[{"name":"Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Department of Human Physiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031209130200200_R1","doi-asserted-by":"crossref","unstructured":"Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d\u2019Arminio MA, Knysz B, Dietrich M, Phillips AN, Lundgren JD: Decline in the AIDS and death rates in the EuroSIDA study: an observational study. 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