# Exercise Regulation of Glucose Homeostasis

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2024 · $684,014

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall hypothesis of this project is that regular physical exercise in mothers is critical for the prevention of
type 2 diabetes and metabolic disease in offspring. Our mouse studies establish that maternal exercise before
and during pregnancy has striking beneficial effects on the metabolic health of both male and female offspring.
These findings have opened a new area of exercise physiology research, suggesting that exercise is an
important tool to combat the development of type 2 diabetes, and underscores the need for scientific
investigation aimed at determining the molecular mechanisms by which maternal exercise improves metabolic
health of offspring. For this purpose, and based on our extensive published and preliminary data, we have
defined four Specific Aims. Specific Aim 1 will investigate the vitamin D receptor (VDR) and TGF2 as central
mediators of maternal exercise effects on offspring metabolic health in liver, skeletal muscle, and other
offspring tissues. This includes experiments that will: a) determine the function of VDR in maternal exercise-
induced hepatic, skeletal muscle, and adipose tissue AMPK/TET signaling, epigenetic changes, and in vivo
glucose homeostasis; b) investigate TGF2 as a maternally derived exercise signal that activates epigenetic
changes and improves offspring phenotype; and c) determine if maternal exercise has wide ranging effects to
improve the function of skeletal muscle and adipose tissues. Specific Aim 2 will determine optimal exercise and
pharmacologic treatments for the improvement of offspring metabolic health. This includes experiments to
define: a) optimal maternal exercise protocols to improve metabolic health; and b) pharmacologic activators
that mimic the beneficial effects of maternal exercise on offspring health. Specific Aim 3 is to identify and
determine the function of novel exercise regulated placental proteins that improve the metabolic health of
offspring, as our initial findings established that placenta is central to transmitting the effects of maternal
exercise to offspring. Aim 3 experiments include: a) investigation of novel placental secretory proteins
increased by maternal exercise; b) fetal tissue destination of these proteins; and c) investigating maternal
exercise effects on placenta spatial and single cell transcriptomics. We have recently made the exciting
discovery that grandmaternal exercise improves the metabolic health of second generation (F2) offspring in
adulthood. Specific Aim 4 will determine the mechanisms by which grandmaternal exercise training enhances
F2 offspring health. This will include investigating: a) maternal exercise effects on F1 sperm and oocytes; b)
mechanisms for improved glucose tolerance in F2 offspring, including studies of skeletal muscle glucose
uptake; and c) effects of grandmaternal exercise on epigenetic regulation of skeletal muscle, liver, and adipose
tissue in F2. This emerging area of exercise physiology re...

## Key facts

- **NIH application ID:** 10773092
- **Project number:** 5R01DK101043-26
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** LAURIE J GOODYEAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $684,014
- **Award type:** 5
- **Project period:** 2013-09-16 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773092

## Citation

> US National Institutes of Health, RePORTER application 10773092, Exercise Regulation of Glucose Homeostasis (5R01DK101043-26). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10773092. Licensed CC0.

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