The Effect of Aerobic Exercise on Insulin Resistance: Narrative review of the Molecular Mechanisms

Sahebi, Farnaz; Azarbayjani, Mohammad Ali; Atashak, Sirvan; Peeri, Maghsoud; Rahmati, Saleh

doi:10.18502/ijdo.v18i2.21650

Volume 18, Issue 2 (6-2026) IJDO 2026, 18(2): 130-144 | Back to browse issues page

‎ 10.18502/ijdo.v18i2.21650

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Sahebi F, Azarbayjani M A, Atashak S, Peeri M, Rahmati S. The Effect of Aerobic Exercise on Insulin Resistance: Narrative review of the Molecular Mechanisms. IJDO 2026; 18 (2) :130-144
URL: http://ijdo.ssu.ac.ir/article-1-1040-en.html

The Effect of Aerobic Exercise on Insulin Resistance: Narrative review of the Molecular Mechanisms

Farnaz Sahebi

, Mohammad Ali Azarbayjani ^*

, Sirvan Atashak

, Maghsoud Peeri

, Saleh Rahmati

Department of Exercise Physiology, CT.C., Islamic Azad University, Tehran, Iran.

Abstract: (158 Views)

Insulin resistance (IR) is a central pathophysiological hallmark of type 2 diabetes mellitus (T2D) and related cardio-metabolic disorders. This narrative review explores the impact of regular physical activity, particularly aerobic and resistance exercise, on the mitigation of IR through various molecular mechanisms. Genetic predispositions, chronic low-grade inflammation, dysregulated circulating metabolites, hormonal imbalances, oxidative stress, and abnormal enzymatic activities collectively contribute to the pathogenesis of IR. Physical activity, especially aerobic exercise, has significant anti-IR effects by modulating inflammatory processes. This includes suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and adipokines (e.g., resistin, visfatin), as well as an increase in anti-inflammatory myokines (e.g., irisin, muscle-derived IL-6) and adiponectin/emilin-1 profiles. These changes create an anti-inflammatory environment that enhances insulin signaling in skeletal muscle, liver, and adipose tissue. Hormonal adjustments, such as improved insulin secretion, beta-cell function, and tissue sensitivity, further support these metabolic adaptations. Additionally, exercise reduces oxidative stress by strengthening antioxidant defenses and inhibiting key IR-promoting enzymes like PTP1B and 11β-HSD1. This preservation of tyrosine phosphorylation of the insulin receptor and downstream IRS-1/PI3K/Akt pathway activation leads to increased GLUT4 translocation and glucose uptake. In summary, regular exercise is a cost-effective, non-pharmacological intervention that targets interconnected molecular factors in the etiology of IR. These diverse effects highlight its therapeutic potential in personalized prevention and management strategies for IR and associated metabolic diseases, warranting its integration into clinical guidelines.

Keywords: Aerobic exercise, Insulin resistance, Molecular mechanisms

Full-Text [PDF 809 kb] (76 Downloads)

Type of Study: Review | Subject: Special
Received: 2024/08/14 | Accepted: 2026/05/10 | Published: 2026/06/1

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