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

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Standard

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. / Haugaard, Steen B.; Andersen, Ove; Madsbad, Sten; Frøsig, Christian; Iversen, Johan; Nielsen, Jens Ole; Wojtaszewski, Jørgen.

In: Diabetes, Vol. 54, No. 12, 2005, p. 3474-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Haugaard, SB, Andersen, O, Madsbad, S, Frøsig, C, Iversen, J, Nielsen, JO & Wojtaszewski, J 2005, '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', Diabetes, vol. 54, no. 12, pp. 3474-83.

APA

Haugaard, S. B., Andersen, O., Madsbad, S., Frøsig, C., Iversen, J., Nielsen, J. O., & Wojtaszewski, J. (2005). 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. Diabetes, 54(12), 3474-83.

Vancouver

Haugaard SB, Andersen O, Madsbad S, Frøsig C, Iversen J, Nielsen JO et al. 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. Diabetes. 2005;54(12):3474-83.

Author

Haugaard, Steen B. ; Andersen, Ove ; Madsbad, Sten ; Frøsig, Christian ; Iversen, Johan ; Nielsen, Jens Ole ; Wojtaszewski, Jørgen. / 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. In: Diabetes. 2005 ; Vol. 54, No. 12. pp. 3474-83.

Bibtex

@article{4fdbfa80a56811dbbee902004c4f4f50,
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",
abstract = "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.",
author = "Haugaard, {Steen B.} and Ove Andersen and Sten Madsbad and Christian Fr{\o}sig and Johan Iversen and Nielsen, {Jens Ole} and J{\o}rgen Wojtaszewski",
note = "PUF 2005 5200 042",
year = "2005",
language = "English",
volume = "54",
pages = "3474--83",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "12",

}

RIS

TY - JOUR

T1 - 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

AU - Haugaard, Steen B.

AU - Andersen, Ove

AU - Madsbad, Sten

AU - Frøsig, Christian

AU - Iversen, Johan

AU - Nielsen, Jens Ole

AU - Wojtaszewski, Jørgen

N1 - PUF 2005 5200 042

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

M3 - Journal article

VL - 54

SP - 3474

EP - 3483

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -

ID: 90179