TY - JOUR
T1 - Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection
AU - Cheney, Laura
AU - Hou, June C.
AU - Morrison, Sidonie
AU - Pessin, Jeffrey
AU - Steigbigel, Roy T.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) Medical Scientist Training Program (MSTP) grant GM00855 (to L. C.) and a Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation pre-doctoral Fellowship (to L. C.). Additional support was provided by grants DK033823, DK020541, and 5-MO1-RR-10710 from the NIH.
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir170
DO - 10.1093/infdis/jir170
M3 - Article
C2 - 21606541
AN - SCOPUS:79957525101
SN - 0022-1899
VL - 203
SP - 1824
EP - 1831
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -