Pancreatic exocrine-beta cell communication: a story of two neighbours
Pancreatic exocrine-beta cell communication: a story of two neighbours
Type 1 diabetes (T1D) occurs due to auto-immune destruction of insulin-producing beta cells. Exogenous insulin replacement is the main treatment, with no cure or known triggers for beta cell damage. Though functionally distinct, the exocrine and endocrine pancreas likely engage in crucial crosstalk. Disruption of the communication can impair pancreatic development and contribute to diseases like T1D. Notably, exocrine dysfunction and inflammation are observed in individuals at risk for or diagnosed with T1D. However, cause-consequence studies are needed to address how exocrine damage affects beta cell growth and function using a living zebrafish model. At 5 days post-fertilization, the zebrafish pancreas contains a vascularized and innervated islet embedded within exocrine tissue.
Therefore, this thesis of Noura Faraj demonstrates how zebrafish model allows real-time analysis of exocrine–beta cell interactions using reporters, advanced microscopy, or label-free imaging. Targeted exocrine disruption is induced via the nifurpirinol–nitroreductase (NFP-NTR) system, allowing subsequent tracking of beta cell changes. Following damage, zebrafish beta cells show increased ER stress and reactive oxygen species levels. Moreover, beta cell numbers decline without signs of apoptosis, alongside macrophage recruitment to the pancreas. Preliminary transcriptomic data suggest that beta cell loss may involve reduced proliferation and the activation of non-apoptotic cell death pathways such as ferroptosis and necroptosis.
In conclusion, exocrine disruption causes beta cell stress and failure, underscoring the importance of exocrine–beta cell communication in early T1D. Further studies may uncover conserved stress pathways in humans, advancing molecular understanding of beta cell decline and supporting the development of preventative strategies.