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Document Type

Abstract

Publication Date

1-14-2026

Abstract

Considering the progressive enhancement of individuals’ quality of life and the concomitant alteration in dietary patterns, the incidence of type 2 diabetes mellitus (T2DM) has experienced a marked upsurge in recent times, increasingly manifesting as a pivotal global public health emergency that necessitates immediate attention. T2DM is a long-term metabolic condition with widespread complications that significantly impact the well-being and lifespan of those affected. Physical activity has been shown to prevent and improve the occurrence and progression of T2DM, and exercise can increase the expression of β-hydroxybutyric acid (β-HB). β-HB is recognized as the primary ketone body (KB) present within the human body. It is mainly produced in the liver, from where it is transported to various peripheral tissues such as the brain, heart, and skeletal muscle, where it is utilized as a vital energy source. Beyond its role as an energy substrate that supports metabolic homeostasis, β-HB also acts as a signaling molecule. Its signaling capabilities extend to influencing processes occurring both at the cell surface and within the intracellular environment. Such functions suggest that β-HB may have a significant role in the development of T2DM and a variety of other human health issues. Method: This review used exercise, β-HB, T2DM, and their complications as the keywords, searched PubMed and Web of science (up to January 2025), and collated them and aiming to highlight the recent research developments concerning β-HB and its implications for T2DM and its related complications. It provides a comprehensive examination of β-HB's biosynthetic pathways, elaborates on its physiological roles, and explores its potential as a therapeutic agent. By detailing these aspects, the manuscript seeks to contribute to a deeper understanding of β-HB’s impact on health and disease, particularly in relation to metabolic disorders like T2DM and the effect of exercise on β-HB. The findings indicate that Exercise can promote β-HB production and β-HB, as an energy metabolism substrate, modulates glucose and lipid metabolism, preserves pancreatic β-cell integrity, and ameliorates insulin resistance (IR). Additionally, β-HB acts as a signaling agent that may improve the control of T2DM and its complications impacting various organs by facilitating the stability of cellular proteins, minimizing oxidative stress, managing inflammatory responses and endoplasmic reticulum (ER) stress, while also modulating mitochondrial biosynthesis, autophagy, and apoptosis. Exercise-generated β-HB may be a potential metabolite for the diagnosis and treatment of T2DM and its complications.

DOI

https://doi.org/10.18122/ijpah.5.1.190.boisestate

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