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

Insulin resistance (IR) is a central pathophysiological hallmark of type ۲ diabetes mellitus (T۲D) 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-۶) and adipokines (e.g., resistin, visfatin), as well as an increase in anti-inflammatory myokines (e.g., irisin, muscle-derived IL-۶) and adiponectin/emilin-۱ 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 PTP۱B and ۱۱β-HSD۱. This preservation of tyrosine phosphorylation of the insulin receptor and downstream IRS-۱/PI۳K/Akt pathway activation leads to increased GLUT۴ 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.

کلیدواژه ها:

Aerobic exercise ، Insulin resistance ، Molecular mechanisms