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Chronic binge alcohol and ovariectomy-mediated impaired insulin responsiveness in SIV-infected female rhesus macaques
Author(s) -
Liz Simon,
Diego José Lira Torres,
Ari Saravia,
Danielle E. Levitt,
Curtis Vande Stouwe,
Heather McGarrah,
Larry Coleman,
Jason Dufour,
Angela M. Amedee,
Patricia E. Molina
Publication year - 2021
Publication title -
american journal of physiology. regulatory, integrative and comparative physiology/american journal of physiology. regulatory, integrative, and comparative physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.266
H-Index - 175
eISSN - 1522-1490
pISSN - 0363-6119
DOI - 10.1152/ajpregu.00159.2021
Subject(s) - simian immunodeficiency virus , medicine , endocrinology , insulin , insulin resistance , endocrine system , viral load , diabetes mellitus , immunology , human immunodeficiency virus (hiv) , hormone
Aging people living with HIV (PLWH), especially postmenopausal women may be at higher risk of comorbidities associated with HIV, antiretroviral therapy (ART), hypogonadism, and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-β in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX) on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Female macaques were administered CBA (12-15 g/kg/wk) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIV mac251 , and initiated on antiretroviral therapy (ART) 2.5 mo postinfection. After 1 mo of ART, macaques were randomized to OVX or sham surgeries ( n = 7 or 8/group), and euthanized 8 mo post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected time points. Pancreatic gene expression and islet morphology were determined at study endpoint. There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG ( P = 0.06). CBA and OVX decreased the expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction that may be exacerbated by alcohol use and ovarian hormone loss.

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