Hoang Thi BN, Luong TV, Dang HNN, Tran HP, Nguyen TT. Revisiting the pancreas-liver axis in diabetes: The emerging role of exosomal miR-375-3p. World J Diabetes 2026; 17(10): 117752 [DOI: 10.4239/wjd.117752]
Corresponding Author of This Article
Trung Tran Nguyen, PhD, Lecturer, Researcher, Nguyen Tat Thanh Hi-Tech Institute, Nguyen Tat Thanh University, 300A Nguyen Tat Thanh, Ho Chi Minh City 700000, Viet Nam. nguyen.trung@ntt.edu.vn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
editorial
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Oct 15, 2026; 17(10): 117752 Published online Oct 15, 2026. doi: 10.4239/wjd.117752
Revisiting the pancreas-liver axis in diabetes: The emerging role of exosomal miR-375-3p
Bich Ngoc Hoang Thi, Thang Viet Luong, Hai Nguyen Ngoc Dang, Hau Phuc Tran, Trung Tran Nguyen
Bich Ngoc Hoang Thi, Department of Cardiology, Gia An 115 Hospital, Ho Chi Minh City 700000, Viet Nam
Thang Viet Luong, Hai Nguyen Ngoc Dang, Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Tasmania, Australia
Hau Phuc Tran, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
Trung Tran Nguyen, Nguyen Tat Thanh Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Viet Nam
Trung Tran Nguyen, Nguyen Tat Thanh University Center for Hi-Tech Development, Saigon Hi-Tech Park, Ho Chi Minh City 700000, Viet Nam
Co-first authors: Bich Ngoc Hoang Thi and Thang Viet Luong.
Author contributions: Hoang Thi BN and Luong TV are co-first authors and contributed equally to the study’s conception, methodology, and drafting of the original manuscript; Dang HNN and Tran HP contributed to the literature review, data interpretation, overall supervision and manuscript writing and editing; Nguyen TT is the corresponding author and contributed to overall supervision, critical revisions, and correspondence. All the authors read and approved the final version of the manuscript.
AI contribution statement: We used ChatGPT solely as a tool for grammar checking and language polishing to improve the clarity and flow of the manuscript. No portion of the Main Text (Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion) was AI-generated. The entire content and all original ideas were developed and written exclusively by the research team. The AI tool was used only for language polishing and stylistic improvements, sometimes for translation. It was not utilized for data analysis or any form of writing assistance. No AI tool participated in the design of the study or the interpretation of the research results. All figures in the manuscript were created using specialized professional software by the authors. We did not use AI to generate any images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Trung Tran Nguyen, PhD, Lecturer, Researcher, Nguyen Tat Thanh Hi-Tech Institute, Nguyen Tat Thanh University, 300A Nguyen Tat Thanh, Ho Chi Minh City 700000, Viet Nam. nguyen.trung@ntt.edu.vn
Received: December 16, 2025 Revised: January 19, 2026 Accepted: February 3, 2026 Published online: October 15, 2026 Processing time: 288 Days and 15.5 Hours
Abstract
Type 2 diabetes mellitus is characterized by progressive β-cell dysfunction and hepatic insulin resistance, yet the molecular mechanisms linking pancreatic stress to impaired hepatic glucose metabolism remain unclear. In this context, Xu et al recently published a study in World Journal of Diabetes that identified a previously unrecognized mode of pancreas-liver communication mediated by exosomal miR-375-3p. Under glucotoxicity conditions, pancreatic β cells release exosomes enriched with miR-375-3p that are taken up by hepatocytes, where they suppress recombination signal binding protein for immunoglobulin kappa J region expression, impair protein kinase B/glycogen synthase kinase signaling, and reduce hepatic glycogen storage. This mechanism extends the classical pancreas-liver axis beyond insulin signaling and highlights small RNA cargo as a regulator of glucose homeostasis. However, the relevance of this pathway in humans, its tissue specificity beyond the liver, and the potential of circulating exosomal miR-375-3p as an early biomarker of β-cell stress remain unclear. This editorial discusses the study’s strengths and limitations and outlines future directions for validating this axis as a diagnostic and therapeutic target in type 2 diabetes mellitus.
Core Tip: Type 2 diabetes mellitus is characterized by progressive β-cell dysfunction and hepatic insulin resistance, yet the molecular signals linking pancreatic stress to impaired liver glucose metabolism remain incompletely defined. Recent evidence has revealed that exosomal miR-375-3p is a novel mediator of pancreas-liver communication, whereby glucotoxic β cells transfer regulatory miRNA cargo to hepatocytes to repress protein for immunoglobulin kappa J region, disrupt protein kinase B/glycogen synthase kinase signaling, and reduce hepatic glycogen storage. This editorial highlighted the conceptual importance of this exosome-miRNAs axis, critically evaluates its current limitations, and discusses its potential implications for understanding disease progression, biomarker development, and therapeutic targeting in type 2 diabetes.
