Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes
Authors' conclusion
Our high-resolution histomorphological analysis of human pancreatic islets from donors with and without diabetes has uncovered details of the cellular origin of islet prohormone peptide processing defects. Reduced beta cell PC1/3 and increased alpha cell PC1/3 in islets from donors with type 1 diabetes pinpointed the functional deterioration of beta cells and the concomitant potential increase in PC1/3 usage for prohormone processing in alpha cells during the pathogenesis of type 1 diabetes. Our finding of PC1/3 loss in beta cells may inform the discovery of new prohormone biomarkers as indicators of beta cell dysfunction, and the finding of elevated PC1/3 expression in alpha cells may encourage the design of therapeutic targets via leveraging alpha cell adaptation in diabetes.
Study context
- Population
- Human pancreas donors from the Network for Pancreatic Organ Donors with Diabetes (nPOD) repository
- Participants
- 54 donors
- Exposure
- Non-diabetic vs autoantibody-positive vs T1D vs T2D donors
- Outcome
- PC1/3 expression patterns in islet alpha, beta and delta cells at different stages of diabetes
Methodological detailsimmunostaining and high-dimensional image analysis, nPOD repository
- Immunostaining and high-dimensional image analysis
- nPOD repository
Main finding
As reported in the abstract
- Alpha and beta cell morphology altered in T1D, incl. decreased alpha and beta cell size
- Insulin-positive and PC1/3-positive islet areas reduced, with reduced % of PC1/3-positive and insulin-positive/PC1/3-positive cells
- PC1/3 and insulin co-localisation reduced
- Glucagon-positive area and % of glucagon-positive and glucagon-positive/PC1/3-positive cells increased
- PC1/3 and glucagon co-localisation increased in T1D
- Somatostatin-positive cell area and staining intensity elevated in recent-onset T1D
Observational data: associations, not effects.
Original publication
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