title: Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection.
abstract: Human immunodeficiency virus (HIV) infection is associated with insulin resistance. HIV type 1 Nef downregulates cell surface protein expression, alters signal transduction, and interacts with the cytoskeleton and proteins involved in actin polymerization. These functions are required for glucose uptake by insulin-stimulated adipocytes. We sought to determine whether Nef alters adipocyte glucose homeostasis. Using radiolabeled glucose, we found that adipocytes exposed to recombinant Nef took in 42% less glucose after insulin stimulation than did control cells. This reduction resulted from a Nef-dependent inhibition of glucose transporter 4 (GLUT4) trafficking, as assessed by means of immunofluorescence microscopy. Immunoblot analysis revealed a decrease in phosphorylation of signal transducing proteins after Nef treatment, and fluorescence microscopy showed a dramatic alteration in cortical actin organization. We conclude that Nef interferes with insulin-stimulated processes in adipocytes. We have identified HIV Nef, which is detectable and antigenic in serum samples from HIV-infected people, as a novel contributor to the development of insulin resistance.
authors: Department of Pharmacological Sciences, State University of New York at Stony Brook, NY 11794-8153, USA.
authors: Laura
authors: L
authors: Cheney
authors: June C
authors: JC
authors: Hou
authors: Sidonie
authors: S
authors: Morrison
authors: Jeffrey
authors: J
authors: Pessin
authors: Roy T
authors: RT
authors: Steigbigel
references: Exp Cell Res. 1999 Jul 10;250(1):112-21
references: 10388525
references: Nat Immunol. 2009 Sep;10(9):1008-17
references: 19648924
references: Exp Cell Res. 2006 Nov 1;312(18):3659-68
references: 16978607
references: J Gen Virol. 1993 Aug;74 ( Pt 8):1581-9
references: 8345349
references: Mol Cell. 1999 Jun;3(6):729-39
references: 10394361
references: J Gen Virol. 2000 Dec;81(Pt 12):2905-2917
references: 11086122
references: J Virol. 2003 Mar;77(5):3041-9
references: 12584329
references: J Virol. 2004 Mar;78(6):3099-109
references: 14990729
references: J Clin Endocrinol Metab. 1992 May;74(5):1045-52
references: 1373735
references: J Virol. 1994 May;68(5):2906-14
references: 8151761
references: J Virol. 2005 Aug;79(15):10053-8
references: 16014965
references: J Virol. 2007 Apr;81(8):3877-90
references: 17267500
references: J Biol Chem. 2004 Jul 16;279(29):30622-33
references: 15123724
references: FASEB J. 2003 Nov;17(14):2025-36
references: 14597672
references: FASEB J. 2002 Aug;16(10):1254-6
references: 12153994
references: Blood. 2001 Nov 1;98(9):2752-61
references: 11675348
references: Virology. 2006 Aug 1;351(2):322-39
references: 16684552
references: J Virol. 2007 Mar;81(6):2777-91
references: 17182689
references: Antivir Ther. 2006;11(6):729-40
references: 17310817
references: J Virol. 2004 Jun;78(11):5745-55
references: 15140972
references: Exp Cell Res. 2002 May 1;275(2):243-54
references: 11969293
references: PLoS One. 2007 Nov 21;2(11):e1212
references: 18030346
references: J Acquir Immune Defic Syndr. 2009 Dec 1;52(4):459-64
references: 19779308
references: Traffic. 2007 Jan;8(1):61-76
references: 17140399
references: J Biol Chem. 2006 Jul 14;281(28):19618-30
references: 16687395
references: FEBS Lett. 1996 Sep 9;393(1):93-6
references: 8804432
references: Arch Intern Med. 2005 May 23;165(10):1179-84
references: 15911733
references: Nat Immunol. 2006 Mar;7(3):302-10
references: 16429138
references: J Biol Chem. 2001 Nov 9;276(45):42436-44
references: 11546823
references: Cell. 1991 May 17;65(4):651-62
references: 2032289
references: J Clin Endocrinol Metab. 1993 Mar;76(3):559-65
references: 8445011
references: Metabolism. 1991 Jun;40(6):651-6
references: 1865829
references: J Immunol. 1995 Dec 1;155(11):5289-98
references: 7594542
references: PLoS One. 2008 Aug 20;3(8):e3003
references: 18714345
references: J Cell Biol. 2004 Dec 6;167(5):903-13
references: 15569716
references: J Biol Chem. 2002 Jan 4;277(1):509-15
references: 11694514
references: J Leukoc Biol. 2003 Nov;74(5):821-32
references: 12960275
references: J Virol. 2003 Apr;77(7):4169-80
references: 12634375
references: J Acquir Immune Defic Syndr. 2009 Apr 15;50(5):499-505
references: 19223782
references: J Clin Invest. 2001 Aug;108(3):371-81
references: 11489930
references: AIDS Res Hum Retroviruses. 2002 Apr 10;18(6):461-7
references: 11958689
references: Mol Biol Cell. 2006 Oct;17(10):4484-93
references: 16914513
references: HIV Med. 2005 Mar;6(2):114-21
references: 15807717
references: J Biol Chem. 2003 Jan 24;278(4):2219-27
references: 12419805
references: AIDS. 2004 Jan 23;18(2):189-98
references: 15075535
references: Diabetes. 2005 Jan;54(1):23-31
references: 15616007
references: J Biol Chem. 2001 Jul 6;276(27):25605-11
references: 11328823