Mohn Research Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
BetaUpreg Research Group, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania.
Commun Biol. 2024 Jul 9;7(1):833. doi: 10.1038/s42003-024-06527-5.
Regeneration, the ability to replace injured tissues and organs, is a phenomenon commonly associated with lower vertebrates but is also observed in mammals, in specific tissues. In this study, we investigated the regenerative potential of pancreatic islets following moderate beta-cell loss in mice. Using a rapid model of moderate ablation, we observed a compensatory response characterized by transient inflammation and proliferation signatures, ultimately leading to the recovery of beta-cell identity and function. Interestingly, this proliferative response occurred independently of inflammation, as demonstrated in ablated immunodeficient mice. Furthermore, exposure to high-fat diet stimulated beta-cell proliferation but negatively impacted beta-cell function. In contrast, an equivalent slower ablation model revealed a delayed but similar proliferative response, suggesting proliferation as a common regenerative response. However, high-fat diet failed to promote proliferation in this model, indicating a differential response to metabolic stressors. Overall, our findings shed light on the complex interplay between beta-cell loss, inflammation, and stress in modulating pancreatic islet regeneration. Understanding these mechanisms could pave the way for novel therapeutic strategies based on beta-cell proliferation.
再生，即替换受伤组织和器官的能力，通常与低等脊椎动物有关，但也存在于哺乳动物的特定组织中。在这项研究中，我们研究了中度β细胞损失后小鼠胰岛的再生潜力。我们利用一种快速的中度消融模型，观察到了一种代偿性反应，其特征是短暂的炎症和增殖特征，最终导致β细胞身份和功能的恢复。有趣的是，正如在消融免疫缺陷小鼠中所证明的那样，这种增殖反应独立于炎症发生。此外，高脂肪饮食刺激β细胞增殖，但对β细胞功能产生负面影响。相比之下，等效的较慢消融模型显示出延迟但相似的增殖反应，表明增殖是一种常见的再生反应。然而，高脂肪饮食未能在该模型中促进增殖，表明对代谢应激的反应不同。总的来说，我们的发现揭示了β细胞损失、炎症和应激在调节胰腺胰岛再生中的复杂相互作用。了解这些机制可能为基于β细胞增殖的新治疗策略铺平道路。
