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Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women.

Authors: Gerena, Y  Skolasky, RL  Velez, JM  Toro-Nieves, D  Mayo, R  Nath, A  Wojna, V 
Citation: Gerena Y, etal., PLoS One. 2012;7(5):e37358. doi: 10.1371/journal.pone.0037358. Epub 2012 May 22.
Pubmed: (View Article at PubMed) PMID:22629383
DOI: Full-text: DOI:10.1371/journal.pone.0037358

BACKGROUND: Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population. OBJECTIVE: To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women. METHODS AND RESULTS: This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (alpha) and full-length or intact (alphabeta)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND. CONCLUSIONS: This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND.


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RGD Object Information
RGD ID: 10403033
Created: 2015-11-04
Species: All species
Last Modified: 2015-11-04
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.