# Clock Control of Muscle Glucose Metabolism and HIF Activity

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $405,972

## Abstract

PROJECT SUMMARY:
Despite recent advances in uncovering the role of circadian clocks in cardiometabolic disease and type-
2 diabetes, a gap remains in our understanding of how nutrient and circadian transcriptional regulators
coordinate responses to environmental stimuli across the 24-hour cycle in a tissue-specific manner.
Our recently published studies uncovered novel reciprocal interactions between the skeletal muscle
circadian clock and the nutrient-sensitive hypoxia-inducible factor (HIF) transcription pathway.
Specifically, our work demonstrated that (i) circadian transcription factors regulate hypoxic HIF1α
activation and anaerobic glycolysis in muscle myotubes, (ii) the muscle circadian clock regulates
genome-wide hypoxic transcription, and (iii) the circadian clock establishes a time-of-day dependent
response to exercise-induced HIF activation in skeletal muscle. Collectively, these studies reveal
coupling of the hypoxia-inducible factor and circadian pathways in order to produce rhythmic adaptation
to hypoxic stress. However, it is still unclear how this coupling acts to regulate transcription and
metabolic flux, and whether in vivo circadian disruption impairs HIF-dependent metabolic
functions, such as glucose disposal in muscle in the context of exercise and diet-induced
obesity. Our present proposed studies will utilize an array of innovative models and techniques to build
upon our current findings to understand the interplay between hypoxic and circadian transcriptional
pathways at the genomic, nutrient-signaling, and whole-animal physiological levels. Overall, these
studies will advance our understanding of the role of circadian clocks in muscle metabolic
function and disease.

## Key facts

- **NIH application ID:** 10237380
- **Project number:** 5R01DK123358-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Clara Bien Peek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,972
- **Award type:** 5
- **Project period:** 2020-08-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237380

## Citation

> US National Institutes of Health, RePORTER application 10237380, Clock Control of Muscle Glucose Metabolism and HIF Activity (5R01DK123358-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10237380. Licensed CC0.

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