Introduction: Type 2 Diabetes Mellitus (T2DM) is a chronic, multi-factorial metabolic disorder characterized by insulin resistance, pancreatic beta-cell dysfunction, and chronic inflammation. In recent years, numerous studies have explored the role of cellular and molecular pathways in the pathophysiology of this disease. This review study aims to comprehensively examine the biological pathways involved in T2DM—including PI3K/Akt, AMPK, NF-κB, JNK, epigenetics, mitochondrial function, and adipokines—and analyze the role of exercise as an effective non-pharmacological intervention in regulating these pathways.
Methods: A systematic search was conducted across PubMed, Scopus, Web of Science, and Google Scholar databases using keywords related to type 2 diabetes, molecular pathways, and exercise. The search period spanned from January 2015 to July 2025. Ultimately, 24 relevant and high-quality articles, including experimental, review, and clinical studies, were selected for final analysis.
Findings: Research indicates that the aforementioned pathways play critical roles in the development of insulin resistance, beta-cell dysfunction, and systemic inflammation. Exercise improves glucose metabolism and reduces inflammation by activating AMPK, enhancing PI3K/Akt signaling, inhibiting NF-κB and JNK, regulating gene expression through epigenetic modifications, increasing mitochondrial biogenesis, and modulating adipokine levels.
Conclusion: As a multi-faceted intervention, exercise has the capacity to target key cellular and molecular pathways associated with T2DM. These findings suggest that designing targeted exercise interventions can play a vital role in the prevention, management, and treatment of type 2 diabetes, paving the way for the development of personalized approaches in future medicine