Browse by author
Lookup NU author(s): Alana Mullins, Xuefei Yu, Dr Anna SmithORCiD, George MercesORCiD, Professor James ShawORCiD, Professor Laura GreavesORCiD, Emeritus Professor Mark Walker, Dr Catherine ArdenORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mitochondrial dysfunction is a key feature of type 2 diabetes and is closely linked to ageing, a major risk factor for the disease. This study investigated islet cell composition and mitochondrial oxidative phosphorylation protein expression in pancreatic tissue from older donors (≥62 years) with and without type 2 diabetes, matched for age, sex, and BMI. Fixed human pancreatic tissue sections were immunolabelled for insulin, glucagon, NDUFB8 (complex I), MTCO1 (complex IV), and VDAC1 (a mitochondrial mass marker) to quantify islet composition and mitochondrial protein levels. A machine learning-based single-cell segmentation pipeline enabled high-resolution profiling of individual cell populations within islets. In type 2 diabetes, islets exhibited an increased alpha:beta cell ratio, altered spatial organisation with fewer beta-beta and more alpha-alpha interactions, and a significantly higher proportion of bi-hormonal cells co-expressing insulin and glucagon. Within beta cells, we observed significant changes in mitochondrial protein expression, including reduced complex I and elevated complex IV levels. Unsupervised clustering of mitochondrial expression patterns identified three distinct beta cell expression clusters. Donors with type 2 diabetes showed a marked shift in the distribution of beta cells across clusters, with increased proportions of beta cells exhibiting low complex I and high complex IV expression. These results highlight significant alterations in islet architecture and mitochondrial protein expression associated with type 2 diabetes, providing new insights into the mechanisms underlying type 2 diabetes.
Author(s): Mullins A, Yu X, Smith ALM, Merces G, Shaw JAM, Greaves LC, Walker M, Arden C
Publication type: Article
Publication status: Published
Journal: Journal of Endocrinology
Year: 2025
Volume: 267
Issue: 1
Print publication date: 23/10/2025
Online publication date: 08/10/2025
Acceptance date: 06/10/2025
Date deposited: 03/11/2025
ISSN (print): 0022-0795
ISSN (electronic): 1479-6805
Publisher: Bioscientifica Ltd
URL: https://doi.org/10.1530/JOE-25-0253
DOI: 10.1530/JOE-25-0253
Data Access Statement: The datasets generated from this study are available from the corresponding author upon reasonable request.
PubMed id: 41059747
Altmetrics provided by Altmetric
