# The Interaction of Diabetes and Estrogen on Skeletal Muscle Bioenergetics

> **NIH VA IK2** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2020 · —

## Abstract

Type 2 Diabetes (T2D) is a major health priority within the VA. More than 24% of Veterans have T2D, twice
the national average. There is an increasing population of female veterans in the VA in the premenopausal age
range. Premenopausal women with T2D have poorer health-related outcomes compared with age-matched
men with T2D. The mechanisms for this sex difference in T2D are unknown. Aerobic power predicts the
incidence of the poor health-related outcomes associated with T2D. T2D negatively impacts aerobic power to a
greater degree in premenopausal women with T2D compared with men with T2D. Aerobic power is partially
dependent on skeletal muscle bioenergetics. This proposal is designed to address a clinically significant
knowledge gap related to women with T2D, to identify potential targets for clinical therapies to improve the
health of women with T2D, and to provide training in several specific methods that will prepare me for a
successful transition to independence.
Aerobic power is partially dependent on skeletal muscle bioenergetics: signaling associated with and measures
of cellular energy balance and mitochondrial biogenesis/function. Estrogen (E2) signaling is reported to be
supportive of skeletal muscle bioenergetics, however, my surprising preclinical data suggest that the
physiological context in which estrogen signaling is studied is important. My pilot data reveal an unexpected
adverse interaction of E2 and diabetes on the regulators of skeletal muscle bioenergetics. My working
hypothesis is that diabetes suppresses E2-mediated support of bioenergetics in skeletal muscle of
reproductive aged female rats. I will address this hypothesis with two specific aims:
Aim 1: To test the impact of the diabetic environment on skeletal muscle E2 signaling and mitochondrial
biogenesis in vitro. This aim will determine impact of diabetes on E2-mediated support of signaling associated
with and measures of cellular energy balance and mitochondrial biogenesis. Through intricate signaling studies
data will be generated to identify the diabetes-associated mechanism(s) that could be targeted to restore
mitochondrial bioenergetics in women with T2D.
Aim 2: To understand whether the disruption of E2 support of skeletal muscle bioenergetics in vivo by diabetes
impairs exercise capacity. This aim will determine the bioenergetic consequences of the diabetes-associated
disruption of E2 support of skeletal muscle through measures of substrate utilization, mitochondrial function,
and aerobic exercise capacity.
This proposal addresses the clinically relevant knowledge gap related to decreased functional status of
premenopausal women with T2D and could identify potential targets for clinical therapies to improve the health
of women with T2D. Through training with my mentors, coursework, and the successful completion of the
project specific aims, I will further develop my knowledge base and skillset in primary cell culture, cellular
signal transduction, and manipul...

## Key facts

- **NIH application ID:** 9850849
- **Project number:** 5IK2BX004533-02
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Rebecca L Scalzo
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850849

## Citation

> US National Institutes of Health, RePORTER application 9850849, The Interaction of Diabetes and Estrogen on Skeletal Muscle Bioenergetics (5IK2BX004533-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9850849. Licensed CC0.

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