Single‐Cell RNA Sequencing Shows Exercise Protects <i>db/db</i> Mouse Pancreatic Injuries by Regulating Endothelial Cell Homeostasis

The prevalence and mortality rates of Type 2 diabetes mellitus (T2DM) continue to increase, imposing a significant burden on individuals and nations worldwide. The pancreas plays an important role in T2DM development, while exercise is a crucial nonpharmacological treatment. Although the pancreas comprises various cell types, current studies on the effects of exercise on diabetes have mainly focused on the beta cells. In this study, we aimed to enhance our understanding of the effects of exercise on other pancreatic cell types. This was aimed at facilitating the comprehensive analysis of the processes and principles by which exercise protects and enhances pancreatic function. Six-week-old male <i>db/db</i> mice were trained on a treadmill at a speed of 9 m/min for 10 weeks (50 min/day, 5 days/week). Single-cell RNA sequencing (scRNA-seq) was performed to analyze cell types in the pancreas. The results showed that exercise improved the body weight and pancreas profile of <i>db/db</i> mice. The scRNA-seq demonstrated that the pancreas was composed of 12 cell types, with obvious changes in endothelial cells (ECs) among all groups. Further subtype analysis suggested that ECs could be annotated into five subtypes, with capillary ECs and unknown EC 1 presenting remarkable differences among the groups. Additionally, Gene Ontology (GO) enrichment analysis showed the roles of regulation of EC proliferation and response to injury for capillary ECs and unknown EC 1, respectively. The two EC subtypes may be involved in the protective effect of exercise against pancreatic injury in <i>db/db</i> mice.