# Alcohol-induced Skeletal Muscle Insulin Insensitivity in SIV/HIV: Myotube-derived Extracellular Vesicle-mediated Mechanisms

> **NIH NIH F30** · LSU HEALTH SCIENCES CENTER · 2022 · $38,605

## Abstract

Abstract
The primary purpose of this Ruth L. Kirschstein NRSA F30 application is to provide the groundwork that will
prepare the applicant for an academic medical career. Much of the applicant’s career development will come
from work in High Priority HIV/AIDS comorbidity-related research, and she will have the invaluable opportunity
to carry out high quality research using a well-established preclinical model of chronic binge alcohol (CBA) and
simian immunodeficiency virus (SIV) infection. At-risk alcohol use is twice as likely in people living with HIV
(PLWH) as it is in the general population. PLWH on antiretroviral therapy (ART) have a near normal life
expectancy, but there is an increase in prevalence of metabolic comorbidities, requiring a need for research
studying pathophysiological mechanisms of metabolic dysregulation in the context of HIV. Studies from our group
have shown that at-risk alcohol use and CBA is associated with impaired insulin/glucose dynamics in PLWH and
in SIV-infected macaques, respectively. Skeletal muscle (SKM) is a major site of insulin-dependent glucose
uptake, and preclinical studies indicate that alcohol decreases SKM insulin sensitivity. Preliminary data
generated for this application suggest that CBA dysregulates proteins in the insulin signaling pathway in SKM,
further indicating that alcohol leads to SKM dysfunction. With previous work from our group demonstrating that
CBA-mediated alterations in myotubes reflect what is seen in SKM, we will utilize cultured myotubes to reflect
changes seen in SKM in our proposed experiments. Extracellular vesicles (EVs) mediate cellular changes in
pathologic and therapeutic conditions by transporting bioactive cargo, including microRNAs (miRNAs), between
cells. miRNAs are small non-coding RNAs that regulate gene expression and are differentially expressed by
CBA and insulin resistance. Preliminary and previous data suggests that CBA leads to lower expression of the
SKM specific miRNA-206 in plasma EVs and the SKM of SIV-infected macaques, and miRNA-206 is implicated
in SKM insulin-dependent glucose uptake. Taken together, our preliminary data and published literature support
the hypothesis, that alcohol-mediated alterations in myotube extracellular vesicle miRNA cargo contribute
to decreased myotube insulin sensitivity in SIV infection. The proposed study will employ a wide variety of
state-of- the-art techniques to test the hypothesis using two specific aims: (1) CBA-administration alters myotube-
derived EV profile in SIV-infected macaques, and (2) myotube-derived EV miRNA cargo of CBA-administered
SIV-infected macaques decreases myotube insulin sensitivity. Findings from the proposed studies will provide
insight on the role of EVs in alcohol-mediated SKM insulin insensitivity in SIV infection. Additionally, the proposed
project aims to illustrate the therapeutic potential of EVs in improving alcohol-mediated SKM dysfunction. With
a strong mentoring team committed to develo...

## Key facts

- **NIH application ID:** 10554094
- **Project number:** 5F30AA029358-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Brianna Leilani Bourgeois
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,605
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554094

## Citation

> US National Institutes of Health, RePORTER application 10554094, Alcohol-induced Skeletal Muscle Insulin Insensitivity in SIV/HIV: Myotube-derived Extracellular Vesicle-mediated Mechanisms (5F30AA029358-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10554094. Licensed CC0.

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