Johar D, Mahmoud K, Zaky S. Perspectives on the bioenergetic dysregulation in insulin-resistant patients comorbid with cancer. World J Transl Med 2026; 12(3): 124147 [DOI: 10.5528/wjtm.124147]
Corresponding Author of This Article
Dina Johar, PhD, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Asma Fahme Street, Heliopolis, Cairo 11757, Egypt. dinajohar@gu.edu.eg
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Biochemistry & Molecular Biology
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review-article
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Johar D, Mahmoud K, Zaky S. Perspectives on the bioenergetic dysregulation in insulin-resistant patients comorbid with cancer. World J Transl Med 2026; 12(3): 124147 [DOI: 10.5528/wjtm.124147]
World J Transl Med. Sep 28, 2026; 12(3): 124147 Published online Sep 28, 2026. doi: 10.5528/wjtm.124147
Perspectives on the bioenergetic dysregulation in insulin-resistant patients comorbid with cancer
Dina Johar, Khaled Mahmoud, Samy Zaky
Dina Johar, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Cairo 11757, Egypt
Khaled Mahmoud, Department of Pharmacognosy, National Research Centre, Giza 12622, Egypt
Samy Zaky, Hepatogastroenterology and Infectious Diseases Department, Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt
Author contributions: Johar D contributed to the conception and design of the study, interpretation of literature data, writing, and generation of graphs; Mahmoud K contributed to revisions; Johar D, Mahmoud K, and Zaky S contributed to discussion and review of the manuscript; Mahmoud K and Zaky S contributed to supervision; and Zaky S contributed to administration; All authors have read and approved the final manuscript.
AI contribution statement: No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Dina Johar, PhD, Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Asma Fahme Street, Heliopolis, Cairo 11757, Egypt. dinajohar@gu.edu.eg
Received: June 9, 2026 Revised: July 19, 2026 Accepted: August 10, 2026 Published online: September 28, 2026 Processing time: 87 Days and 16.1 Hours
Abstract
Insulin resistance, a pathophysiological response in metabolic syndrome, raises cancer risk. Mitochondrial dysfunction is a hallmark of cancer. The mitochondrial energetic profile of platelets in patients with cancer who have insulin resistance is unclear. Similarly, the profile of mitochondrial dysfunction in type 2 diabetes (T2-D) has not yet been published. The transmembrane protein in human adipose tissue known as dipeptidyl peptidase 4 (DPP4) is associated with T2-D secondary to obesity. Furthermore, DPP4 has been implicated in cancer pathogenesis. Studies have shown a connection between obesity and cancer. However, whether DPP4 inhibition ameliorates insulin resistance in patients with cancer has not been elucidated. This perspective aims to explore how platelet mitochondria fail in patients with cancer who have insulin resistance, discuss how blocking DPP4 might antagonize insulin resistance in cancer, and describe a cell culture model for obesity and insulin resistance. The available literature supports the proposal that patients with cancer and insulin resistance (or T2-D) have less active mitochondria in their platelets than patients with cancer without insulin resistance or healthy individuals. The platelet mitochondrial bioenergetic profile may signal early mitochondrial dysfunction in patients with cancer and insulin resistance. The proposed model is applicable to patients with T2-D and obesity.
Core Tip: This perspective proposes that among patients with cancer, those with insulin resistance exhibit reduced platelet mitochondrial bioenergetics compared with cancer patients without insulin resistance or healthy controls and that platelet mitochondrial profiling may serve as an early marker of mitochondrial dysfunction in this population. It further hypothesizes that dipeptidyl peptidase 4 inhibition may ameliorate insulin resistance in cancer patients and proposes a cell culture model to test this hypothesis. The article’s clinical relevance lies in potentially identifying non-invasive biomarkers for metabolic dysfunction in patients with cancer and exploring dipeptidyl peptidase 4 (DPP4) inhibitors as therapeutics. Strengths include the integration of cancer biology, metabolic syndrome pathophysiology, and mitochondrial bioenergetics and the proposal of testable frameworks.
