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Review
. 2025 Jul 7;137(2):184-204.
doi: 10.1161/CIRCRESAHA.125.325532. Epub 2025 Jul 3.

Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise

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Free article
Review

Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise

Katie L Whytock et al. Circ Res. .
Free article

Abstract

Skeletal muscle is essential for movement and maintaining energy homeostasis and is the primary tissue for insulin-stimulated glucose uptake. Skeletal muscle is composed of various cell types that help to govern the delivery, transport, and metabolism of nutrients to and within the tissue. Dysregulation of these processes can result in impaired insulin-stimulated glucose uptake and dysglycemia-insulin resistance and type 2 diabetes. Acute exercise and chronic exercise training provide a robust stimulus to improve nutrient delivery, nutrient transport into a cell, and subsequent storage and oxidation to help improve insulin sensitivity. This review details the molecular mechanisms of skeletal muscle insulin resistance and how exercise counteracts these defects, highlighting the key role of exercise in muscle health and disease.

Keywords: exercise; glucose; homeostasis; insulin resistance; muscle, skeletal.

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Conflict of interest statement

None.