Research Paper: Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption

Here, we investigated the regenerative response of pancreatic islets following moderate beta-cell loss in mice using two diffenet models: one rapid beta-cell targeted synchronous cell death by using the RIPDTR model, and one slow heterogeneous cell death by using streptozotocin (STZ).

We showed that:

in the rapid cell death model (RIPDTR):
1. a compensatory response characterized by transient inflammation and proliferation signatures, ultimately leading to the recovery of beta-cell identity and function.
2. this proliferative response occurred independently of inflammation, as demonstrated in ablated immunodeficient mice.
3. exposure to high-fat diet stimulated beta-cell proliferation but negatively impacted beta-cell function.
in the slow cell death model (STZ):
1. a delayed but similar proliferative response, suggesting proliferation as a common regenerative response.
2. high-fat diet failed to promote proliferation in this model, indicating a differential response to metabolic stressors.