# Exercise, Exosomes, and Metabolic Health in Type-2 Diabetes

> **NIH NIH U54** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $464,737

## Abstract

PROJECT SUMMARY/ABSTRACT
Native Hawaiians and other Pacific Islanders (NHOPI) are disproportionately affected by type 2 diabetes
(T2DM), with a two-fold higher prevalence than Whites in Hawaii. T2DM is characterized by hyperglycemia due
to defective insulin action in metabolic tissues, including liver, skeletal muscle, and adipose tissue. Exercise is
an effective intervention to improve glycemic control and reduce the risk of developing T2DM, yet even this risk
reduction is lower in NHOPI than Whites. One important component of addressing the health disparities of
T2DM is to better understand the molecular mechanisms by which exercise increases insulin sensitivity.
Almost all cells release a class of nano-sized extracellular vesicles, called exosomes, which circulate widely
throughout the body. These exosomes carry cellular proteins, RNAs, and lipids from their cell of origin and
signal recipient cells through the release of their cargo. Recent evidence suggests that many exercise-induced
signaling molecules released from skeletal muscle (SkM) are transported in exosomes, and acute exercise
increases the number of these circulating exosomes. In pre-clinical studies, sedentary mice injected with
exosomes isolated from the SkM of exercise-trained mice show improved glucose tolerance and insulin
sensitivity. However, there are no reported studies on how exercise stimulates SkM exosome release or affects
their cargo contents, and it is poorly understood how exercise-induced SkM exosomes increase insulin
sensitivity. The objective of the proposed project is to elucidate the mechanism by which exercise-induced
SkM exosomes modulate insulin sensitivity and glucose metabolism of major metabolic tissues. Our
preliminary studies have identified the exocyst protein complex as a potential link between SkM metabolism
and exosome production. We have found that exocyst activity in SkM cells is highly responsive to insulin and
contraction signaling, and in other tissues, the exocyst regulates exosome production. Our central hypothesis
is that exercise stimulates the exocyst-dependent release of exosomes in SkM, which deliver muscle-derived
factors increasing insulin sensitivity in major metabolic tissues.
To test this hypothesis, we propose the following Aims: (1) Determine how exercise stimulates exosome
release in SkM cells; (2) Identify the molecular cargo and recipient tissues of exercise-induced SkM exosomes;
(3) Determine the signaling mechanism by which SkM-derived exosomes increase post-exercise insulin
sensitivity in models of insulin resistance. This project brings together state-of-the-art in vitro and in vivo
approaches for the first comprehensive molecular study of SkM-derived exosomes and how they regulate
insulin sensitivity and glucose metabolism of major metabolic tissues. These investigations lay the pre-clinical
foundation for therapeutic approaches with SkM exosomes, and may lead to the development of improved
exercise intervention guidelines...

## Key facts

- **NIH application ID:** 10556971
- **Project number:** 2U54MD007601-36
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Noemi Polgar
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $464,737
- **Award type:** 2
- **Project period:** 1997-09-23 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556971

## Citation

> US National Institutes of Health, RePORTER application 10556971, Exercise, Exosomes, and Metabolic Health in Type-2 Diabetes (2U54MD007601-36). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10556971. Licensed CC0.

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