RGD Reference Report - Soluble and cell-associated insulin receptor dysfunction correlates with severity of HAND in HIV-infected women. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

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.
RGD ID: 10403033
Pubmed: PMID:22629383   (View Abstract at PubMed)
PMCID: PMC3358319   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0037358   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
AIDS Dementia Complex severityIEP 10403033protein:increased expression:cerebrospinal fluid and plasmaRGD 
AIDS Dementia Complex severityIDA 10403033protein:decreased tyrosine phosphorylation:cerebrospinal fluid and leukocyteRGD 
AIDS Dementia Complex severityISOINSR (Homo sapiens)10403033; 10403033protein:increased expression:cerebrospinal fluid and plasmaRGD 
AIDS Dementia Complex severityISOIRS1 (Homo sapiens)10403033; 10403033protein:decreased tyrosine phosphorylation:cerebrospinal fluid and leukocyteRGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)
Irs1  (insulin receptor substrate 1)

Genes (Mus musculus)
Insr  (insulin receptor)
Irs1  (insulin receptor substrate 1)

Genes (Homo sapiens)
INSR  (insulin receptor)
IRS1  (insulin receptor substrate 1)


Additional Information