# STIM1 and metabolic flexibility

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $575,706

## Abstract

The prevalence of metabolic diseases such as insulin resistance, diabetes and obesity are reaching
epidemic proportions in the US. Physical inactivity and overnutrition are major contributors to these
conditions. An increased understanding of how physical activity and fuel supply links skeletal muscle
with whole body metabolism is likely to yield important mechanistic insights into metabolic disease
and to contribute to the development of novel therapeutic strategies. Calcium signaling in skeletal
muscle is critical for muscle contraction, metabolism, and gene expression. The role of calcium entry
has been offered as a mechanism for controlling long-term signaling events such as limiting fatigue
during exercise. Our research centers on the role of stromal interaction molecule 1 (STIM1), a
calcium sensor required for store-operated calcium entry (SOCE), as a key regulator of skeletal
muscle calcium signaling. Our current program is focused on the role of STIM1 in oxidative
metabolism. Our preliminary data demonstrate that loss of STIM1 alters oxidative metabolism and
impairs muscle performance. Here, we will establish the specific changes in metabolism produced by
changes in STIM1 signaling and establish the mechanisms through which STIM1 influences muscle
metabolism. Specific Aims proposed in this application include: to determine how STIM1 regulates
metabolic flexibility; to determine how STIM1 regulates mitochondrial calcium signaling and function;
and to determine whether MAP4K4 regulates STIM1 signaling and skeletal muscle metabolism. We
will use methodologies that include genetically modified mouse models of STIM1, high resolution
calcium imaging, bioenergetics, and metabolomics to address these aims. The studies we propose
may provide novel insight to the role of calcium in regulating the metabolic flexibility of skeletal
muscle and are likely to have significant implications for the treatment of impaired muscle metabolism
associated with diabetes mellitus and other metabolic diseases.

## Key facts

- **NIH application ID:** 9895772
- **Project number:** 5R01DK109911-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** DEBORAH M MUOIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $575,706
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895772

## Citation

> US National Institutes of Health, RePORTER application 9895772, STIM1 and metabolic flexibility (5R01DK109911-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9895772. Licensed CC0.

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