Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women.
<h4>Background</h4>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 treatm...
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2012
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oai:doaj.org-article:1389389b84eb4c969073250ad73ebc412021-11-18T07:17:50ZSoluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women.1932-620310.1371/journal.pone.0037358https://doaj.org/article/1389389b84eb4c969073250ad73ebc412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22629383/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods and results</h4>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 (α) and full-length or intact (αβ)] 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.<h4>Conclusions</h4>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.Yamil GerenaRichard L SkolaskyJoyce M VelezDianedis Toro-NievesRaul MayoAvindra NathValerie WojnaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37358 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Yamil Gerena Richard L Skolasky Joyce M Velez Dianedis Toro-Nieves Raul Mayo Avindra Nath Valerie Wojna Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| description |
<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods and results</h4>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 (α) and full-length or intact (αβ)] 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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Yamil Gerena Richard L Skolasky Joyce M Velez Dianedis Toro-Nieves Raul Mayo Avindra Nath Valerie Wojna |
| author_facet |
Yamil Gerena Richard L Skolasky Joyce M Velez Dianedis Toro-Nieves Raul Mayo Avindra Nath Valerie Wojna |
| author_sort |
Yamil Gerena |
| title |
Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| title_short |
Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| title_full |
Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| title_fullStr |
Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| title_full_unstemmed |
Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. |
| title_sort |
soluble and cell-associated insulin receptor dysfunction correlates with severity of hand in hiv-infected women. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/1389389b84eb4c969073250ad73ebc41 |
| work_keys_str_mv |
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