The emerging role of pancreatic exocrine fibrosis as a common aetiological driver of islet dysfunction and diabetes: opportunities for novel disease-modifying interventions – published online 10/02/2026

Nicole Kattner, Ayat Bashir, James A. M. Shaw

Involvement of the exocrine pancreas, including fibrosis, is present in all types of diabetes. In this review, Kattner et al (https://doi.org/10.1007/s00125-026-06678-6) summarise several aspects of pancreas pathology, including the distribution and extent of collagen deposition in type 3c, type 2 and type 1 diabetes. Pancreatic stellate cells (PSCs) and macrophages in the presence of elevated tissue TGF-β are recognised mediators of pancreatic exocrine fibrosis. The authors propose that a vicious cycle of TGF-β-driven profibrotic signalling involving PSCs, macrophages and endocrine cells leads to islet dysfunction and diabetes. Evidence in support of this ‘cycle’ is presented, but they also stress the need for further dynamic studies to confirm causality and potential reversibility. Antifibrotic agents targeting TGF-β are already established in clinical practice for non-pancreatic disease, with studies in pancreatitis underway. The authors emphasise the importance of optimally-designed clinical trials using established and novel agents targeting profibrotic signalling to test the potential for improving glycaemic status initially in type 3c diabetes. The figures from this review are available as a downloadable slideset.

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