The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity
Authors' conclusion
The fibrinolytic system is upregulated in islets with hIAPP aggregation. Plasmin rapidly degrades hIAPP, limiting its aggregation into amyloid and thus protecting beta cells from hIAPP-induced toxicity. Thus, increasing islet plasmin activity might be a strategy to limit beta cell loss in type 2 diabetes.
Study context
- Population
- Isolated islets from hIAPP transgenic and non-transgenic mice; primary islet endothelial cells, bone marrow-derived macrophages (BMDM), INS-1 cells; islets from donors with and without T2D
- Outcome
- Measured effects
Main finding
As reported in the abstract
- Islet Plat expression and plasmin activity increased with amyloid deposition in transgenic mouse islets (n=5)
- p≤0.01
- Not observed in non-transgenic islets; blocked by Congo Red (n=4)
- p≤0.01
- Plat expression increased in BMDM and INS-1 cells after hIAPP exposure vs vehicle (n=4), not in islet endothelial cells
- p≤0.05
- Plasmin restored hIAPP-induced loss of INS-1 cell viability (n=5)
- p≤0.01
- PLAT expression increased in islets from donors with T2D (n=4) vs without T2D (n=7)
- 2.4-fold; p≤0.05
Original publication
The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity. Diabetologia. Published 9 September 2024. doi:10.
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