Linked Life Data

16306364

Source:http://linkedlifedata.com/resource/pubmed/id/16306364

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-11-24
pubmed:abstractText
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 (NOGM(ins)). Skeletal muscle biopsies, obtained from 18 lipodystrophic nondiabetic patients (LIPO) and 18 nondiabetic patients without lipodystrophy (NONLIPO) before and during hyperinsulinemic (40 mU.m(-2).min(-1))-euglycemic clamps, were analyzed for insulin signaling effectors. All patients were on HAART. Both LIPO and NONLIPO patients were normoglycemic (4.9 +/- 0.1 and 4.8 +/- 0.1 mmol/l, respectively); however, NOGM(ins) was reduced by 49% in LIPO patients (P < 0.001). NOGM(ins) correlated positively with insulin-stimulated glycogen synthase activity (I-form, P < 0.001, n = 36). Glycogen synthase activity (I-form) correlated inversely with phosphorylation of glycogen synthase sites 2+2a (P < 0.001, n = 36) and sites 3a+b (P < 0.001, n = 36) during clamp. Incremental glycogen synthase-kinase-3alpha and -3beta phosphorylation was attenuated in LIPO patients (Ps < 0.05). Insulin-stimulated Akt Ser473 and Akt Thr308 phosphorylation was decreased in LIPO patients (P < 0.05), whereas insulin receptor substrate-1-associated phosphatidylinositol (PI) 3-kinase activity increased significantly (P < 0.001) and similarly (NS) in both groups during clamp. Thus, low glycogen synthase activity explained impaired NOGM(ins) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3474-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16306364-Acquired Immunodeficiency Syndrome, pubmed-meshheading:16306364-Adult, pubmed-meshheading:16306364-Antiretroviral Therapy, Highly Active, pubmed-meshheading:16306364-Cholesterol, pubmed-meshheading:16306364-Fatty Acids, Nonesterified, pubmed-meshheading:16306364-Glucose, pubmed-meshheading:16306364-Glycogen Synthase, pubmed-meshheading:16306364-HIV-Associated Lipodystrophy Syndrome, pubmed-meshheading:16306364-Humans, pubmed-meshheading:16306364-Insulin, pubmed-meshheading:16306364-Middle Aged, pubmed-meshheading:16306364-Muscle, Skeletal, pubmed-meshheading:16306364-Oxidation-Reduction, pubmed-meshheading:16306364-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16306364-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16306364-RNA, Viral, pubmed-meshheading:16306364-Signal Transduction, pubmed-meshheading:16306364-Triglycerides, pubmed-meshheading:16306364-Viral Load
pubmed:year
2005
pubmed:articleTitle
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.
pubmed:affiliation
Department of Infectious Diseases, Clinical Research Unit 136, Hvidovre University Hospital, DK 2650 Hvidovre, Copenhagen, Denmark. sbhau@dadlnet.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't