Stressed β-cells contribute to loss of peri-islet extracellular matrix in type 1 diabetes.

ABSTRACT:

Introduction

Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing β-cells in pancreatic islets. The peri-islet extracellular matrix (ECM) is a complex protein barrier that is lost in T1D, in part due to infiltrating immune cells. The contribution of stressed β-cells to ECM degradation during T1D remains unclear.

Methods

To bridge this gap, we used 12-15-week-old NOD mice and pancreas sections from healthy, ≥2 autoantibody positive (Aab+), and recent onset T1D donors. We focused on MMP-3 due to its role in degrading type IV collagen (COL IV) in the peri-islet ECM.

Results

Treatment with proinflammatory cytokines or hyperglycemia increased MMP-3 gene expression and protein levels in mouse and human islets. In NOD pancreas sectio

SUBMITTER: Johansen CG 

PROVIDER: S-EPMC12549269 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature