Perez-Serna Atenea A, Guzman-Llorens Daniel, Dos Santos Reinaldo S, Marroqui Laura
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández de Elche, 03202 Elche, Alicante, Spain.
CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain.
Biomedicines. 2025 Jan 17;13(1):223. doi: 10.3390/biomedicines13010223.
Diabetes is a chronic metabolic disorder whose prevalence increases every year, affecting more than 530 million adults worldwide. Type 1 (T1D) and type 2 diabetes (T2D), the most common forms of diabetes, are characterized by the loss of functional pancreatic β-cells, mostly due to apoptosis. B-cell leukemia/lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), two anti-apoptotic proteins belonging to the Bcl-2 family, are crucial for regulating the intrinsic pathway of apoptosis. However, over the years, they have been implicated in many other cellular processes, including intracellular Ca homeostasis and the regulation of mitochondrial metabolism. Thus, understanding the biological processes in which these proteins are involved may be crucial to designing new therapeutic targets. This review summarizes the roles of Bcl-2 and Bcl-xL in apoptosis and metabolic homeostasis. It focuses on how the dysregulation of Bcl-2 and Bcl-xL affects pancreatic β-cell function and survival, and the consequences for diabetes development.
糖尿病是一种慢性代谢紊乱疾病,其患病率逐年上升,全球有超过5.3亿成年人受其影响。1型糖尿病(T1D)和2型糖尿病(T2D)是最常见的糖尿病类型,其特征是功能性胰腺β细胞丧失,主要原因是细胞凋亡。B细胞白血病/淋巴瘤2(Bcl-2)和B细胞淋巴瘤-超大(Bcl-xL)是属于Bcl-2家族的两种抗凋亡蛋白,对调节细胞凋亡的内在途径至关重要。然而,多年来,它们还与许多其他细胞过程有关,包括细胞内钙稳态和线粒体代谢的调节。因此,了解这些蛋白质所参与的生物学过程可能对设计新的治疗靶点至关重要。本综述总结了Bcl-2和Bcl-xL在细胞凋亡和代谢稳态中的作用。它重点关注Bcl-2和Bcl-xL的失调如何影响胰腺β细胞功能和存活,以及对糖尿病发展的影响。