Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection

Laura Cheney, June C. Hou, Sidonie Morrison, Jeffrey E. Pessin, Roy T. Steigbigel

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 insulinstimulated 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.

Original languageEnglish (US)
Pages (from-to)1824-1831
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number12
DOIs
StatePublished - Jun 15 2011

Fingerprint

Virus Diseases
Adipocytes
Insulin Resistance
HIV
Glucose
Fluorescence Microscopy
Actins
nef Gene Products
Insulin
Facilitative Glucose Transport Proteins
Cytoskeleton
Polymerization
HIV-1
Signal Transduction
Membrane Proteins
Homeostasis
Down-Regulation
Phosphorylation
Serum
Proteins

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection. / Cheney, Laura; Hou, June C.; Morrison, Sidonie; Pessin, Jeffrey E.; Steigbigel, Roy T.

In: Journal of Infectious Diseases, Vol. 203, No. 12, 15.06.2011, p. 1824-1831.

Research output: Contribution to journalArticle

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