# Targeting timing of food intake as a novel strategy against disruption of blood pressure circadian rhythm in diabetes

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $601,123

## Abstract

The normal blood pressure (BP) circadian rhythm is essential to human health, as morning BP
surge is associated with increased incidence of life-threatening cardiovascular events. Moreover, disruption
of BP circadian rhythm, which occurs in up to 75% of diabetic patients, is emerging as an index for future
target organ injury and poor cardiovascular outcomes. However, the mechanism by which BP circadian
rhythm is disrupted in diabetes is largely unknown, and an effective strategy to restore the disrupted BP
circadian rhythm in diabetes has not yet been identified. Our preliminary studies found that by limiting the
time of food available to the active period (ATRF) provided striking protection of the diabetic db/db mice
from the severe disruption of BP circadian rhythm. Moreover, BMAL1, an obligatory clock gene, is required
for and glucagon-like peptide-1 (GLP-1) receptor activation mimics the protection of BP circadian rhythm by
ATRF. These intriguing findings suggest that ATRF can serve as a novel strategy to promote normal BP
circadian rhythms, thus significantly improving the cardiovascular prognosis of diabetic patients. The
current proposal will examine this new exciting possibility by testing the specific hypothesis that active time-
restricted feeding (ATRF) or GLP-1 activation restores normal smooth muscle and renal BMAL1 and
sympathetic oscillations thus protects diabetic mice from disruptions of blood pressure circadian rhythm.
The three specific aims are 1). Determine the mechanism by which BMAL1 is dysregulated in diabetes and
restored by ATRF. 2). Test the hypothesis that ATRF protects BP circadian rhythm via smooth muscle and
renal BMAL1 in diabetes. 3). Define ATRF as a novel chrononutritional therapy and targeting GLP-1 as a
new pharmacological therapy to protect BP circadian rhythm in diabetes. We will monitor the circadian
rhythms of BP, food intake, BMAL1 regulation, vascular smooth muscle function and signaling, renal
function, and sympathetic regulation under ad libitum and ATRF feeding regimens. The various mouse
models will be used are diabetic db/db mice, db/db-per2Luc mice, high-fat diet fed mice, smooth muscle and
renal BMAL1 knockout mice.

## Key facts

- **NIH application ID:** 10308681
- **Project number:** 5R01HL141103-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** MING C GONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $601,123
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308681

## Citation

> US National Institutes of Health, RePORTER application 10308681, Targeting timing of food intake as a novel strategy against disruption of blood pressure circadian rhythm in diabetes (5R01HL141103-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10308681. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*