# Genomic Basis for the Circadian Regulation of B-cell Function and Glucose Homeostasis

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2020 · $40,864

## Abstract

Project Summary
The circadian timing system is programmed by an autoregulatory transcription feedback loop present in brain
and peripheral tissues that coordinates metabolic processes with the sleep-wake cycle. Epidemiologic, clinical,
and genetic studies indicate circadian disruption as an emerging risk factor in the development of diabetes.
Our lab has demonstrated that genetic abrogation of the pancreatic β cell clock leads to acute hypoinsulinemic
diabetes, and that insulin secretion exhibits basal and incretin-stimulated circadian regulation across the sleep-
wake cycle. A remaining question is: How does the core circadian transcription mechanism modulate
response to glucose and insulin secretagogues over the 24-hr timescale? Evidence from clock mutant
pancreatic β-cells suggests that loss of clock activators produces impaired glucose-stimulated insulin secretion
and broad changes in transcriptional activity at β-cell enhancers. These changes in transcription include
pathways that intersect with those regulated by cAMP agonists, including the incretin hormones associated
with meal-related insulin secretion. Indeed, islets stimulated with a glucagon-like peptide 1/cAMP agonist
exhibited pronounced time-of-day dependent transcriptional and insulin secretion responses. The scientific
premise of my present proposal is that the circadian clock controls time-of-day-dependent differences in the
response to nutrient and meal-associated insulin secretagogues through the rhythmic regulation of β cell
chromatin, in turn impacting glucose homeostasis throughout life. The studies in this proposal will provide new
insight into the molecular pathophysiology underlying impaired glucose tolerance following circadian disruption
in shiftwork and states of sleep perturbation.

## Key facts

- **NIH application ID:** 9836846
- **Project number:** 5F30DK116481-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Benjamin John Weidemann
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,864
- **Award type:** 5
- **Project period:** 2017-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836846

## Citation

> US National Institutes of Health, RePORTER application 9836846, Genomic Basis for the Circadian Regulation of B-cell Function and Glucose Homeostasis (5F30DK116481-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836846. Licensed CC0.

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