# Exercise regulation of glucose homeostasis

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2020 · $654,517

## Abstract

PROJECT SUMMARY/ABSTRACT
The rates of obesity and type 2 diabetes are increasing at alarming rates in the United States and throughout
the world. Regular physical activity can prevent or delay the onset of type 2 diabetes, and at least part of the
mechanism for these important effects of exercise is the beneficial role it plays on whole body and tissue
glucose homeostasis. The long-term goal of this project is to understand the molecular mechanisms by which
exercise exerts beneficial effects on glucose homeostasis and metabolic health. Emerging data now suggest
that exercise performed by mothers before and during pregnancy can have important beneficial effects on
offspring health. While it has been known that suboptimal maternal diets, such as a high fat diet, can negatively
affect offspring health, the effects of maternal exercise have not been well explored. Studies from the current
funding cycle of this award have established that maternal (F0 generation) exercise training improves offspring
(F1 generation) metabolic health, including glucose tolerance and insulin sensitivity, and can abolish the
detrimental effects of maternal high fat feeding on offspring metabolic health. Interestingly, these studies found
that paternal exercise also has profound effects on offspring (F1) metabolic health, ameliorating the detrimental
effects of paternal high fat feeding on offspring glucose tolerance, fat mass, and hepatocyte glucose
production. Mouse studies have shown that improved metabolic function of the liver appears to be a major
mechanism mediating the beneficial effects of maternal exercise on offspring health. For paternal exercise,
preliminary data suggest that adaptations to both liver and muscle are major mechanisms for the beneficial
effects of paternal exercise on offspring health. The focus of this project for the coming five years is to
understand the mechanisms underlying these beneficial effects. There is also evidence that the detrimental
effects of poor maternal (F0) diet can propagate through multiple generations (F2). Whether maternal exercise
can reverse these detrimental effects of diet on later generations of offspring (F2) is not known. The overall
hypothesis of this project is that maternal and paternal exercise training improves whole-body and tissue
metabolism in male and female offspring and that epigenetic modifications mediate these important effects of
exercise. There are three specific aims: 1) To determine the mechanisms by which maternal exercise training
improves the metabolic phenotype of F1 offspring liver, 2) To determine the effects of grand-maternal exercise
training on F2 metabolic health, 3) To determine the effects of paternal exercise training on F1 offspring
metabolic health. These studies could result in a new paradigm whereby maternal and paternal exercise are
viewed as central in promoting the metabolic health of offspring, reducing the risk of type 2 diabetes in future
generations.

## Key facts

- **NIH application ID:** 9837430
- **Project number:** 5R01DK101043-22
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** LAURIE J GOODYEAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $654,517
- **Award type:** 5
- **Project period:** 2013-09-16 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837430

## Citation

> US National Institutes of Health, RePORTER application 9837430, Exercise regulation of glucose homeostasis (5R01DK101043-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9837430. Licensed CC0.

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