Journal of Isfahan Medical School

Journal of Isfahan Medical School

Molecular and Cellular Pathways Involved in the Pathophysiology of Type 2 Diabetes and the Role of Exercise in Their Regulation

Document Type : Review Article

Authors
Sedigheh Hosseinpour Delavar 1
Nasrin Poroun 2
Somayeh Bakhtiari dehbalae 2
Parsa Forghani 3
1 Department of Exercise Physiology،Ker.C,.IslamicAzad University، Kermanshah، Iran
2 PhD Student Department of Exercise Physiology, Ker.C., Islamic Azad University, Kermanshah, Iran
3 Kinesioligy and Health Sciences Student, Faculty of Health, York University, Toronto, Ontario, Canada
10.48305/jims.v43.i845.1864
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a chronic, multifactorial metabolic disorder characterized by insulin resistance, pancreatic β‑cell dysfunction, and chronic low‑grade inflammation. The aim of this systematic review was to comprehensively examine the key cellular and molecular pathways involved in type 2 diabetes and to evaluate the role of exercise in regulating these pathways as an effective non‑pharmacological intervention.
Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar. Studies published between January 2015 and July 2025 that investigated cellular and molecular pathways related to type 2 diabetes and/or the effects of exercise on these pathways were included. Study selection and data extraction were performed based on predefined inclusion and exclusion criteria. Data related to molecular pathways, metabolic outcomes, and exercise effects were qualitatively extracted and synthesized.
Findings: A total of 21 studies of acceptable methodological quality were included in the final analysis. The findings indicated that dysregulation of the PI3K/Akt, AMPK, NF‑κB, and JNK signaling pathways, along with epigenetic alterations, mitochondrial dysfunction, and abnormal adipokine secretion, play a central role in the development of insulin resistance, β‑cell dysfunction, and chronic inflammation in type 2 diabetes. Exercise improves glucose metabolism and insulin sensitivity through activation of AMPK, enhancement of PI3K/Akt signaling, inhibition of NF‑κB and JNK pathways, epigenetic regulation of gene expression, increased mitochondrial biogenesis, and modulation of adipokine profiles. Heterogeneity in study designs, exercise modalities and intensities, and outcome measures limited direct comparison of findings, and no meta‑analysis was performed.
Conclusion: Exercise, as a multifaceted therapeutic strategy, is capable of simultaneously targeting multiple cellular and molecular pathways involved in type 2 diabetes. These findings support the role of targeted exercise interventions in the prevention, management, and treatment of type 2 diabetes and may facilitate the development of personalized approaches in future medical practice.

Highlights

Sedigheh Hosseinpour Delavar: Google Scholar

Keywords
Type 2 diabetes mellitus
Molecular pathways
Exercise
Insulin resistance

Subjects

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Journal of Isfahan Medical School
Volume 43, Issue 845
1st Week, March
March and April 2026
Pages 1864-1876

  • Receive Date 05 January 2026
  • Accept Date 07 February 2026