» Articles » PMID: 39857806

Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function

Overview
Journal Biomedicines
Date 2025 Jan 25
PMID 39857806
Authors
Affiliations
Soon will be listed here.
Abstract

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.

References
1.
Scorilas A, Kyriakopoulou L, Yousef G, Ashworth L, Kwamie A, Diamandis E . Molecular cloning, physical mapping, and expression analysis of a novel gene, BCL2L12, encoding a proline-rich protein with a highly conserved BH2 domain of the Bcl-2 family. Genomics. 2001; 72(2):217-21. DOI: 10.1006/geno.2000.6455. View

2.
Gurzov E, Germano C, Cunha D, Ortis F, Vanderwinden J, Marchetti P . p53 up-regulated modulator of apoptosis (PUMA) activation contributes to pancreatic beta-cell apoptosis induced by proinflammatory cytokines and endoplasmic reticulum stress. J Biol Chem. 2010; 285(26):19910-20. PMC: 2888402. DOI: 10.1074/jbc.M110.122374. View

3.
Yang J, Vais H, Gu W, Foskett J . Biphasic regulation of InsP3 receptor gating by dual Ca2+ release channel BH3-like domains mediates Bcl-xL control of cell viability. Proc Natl Acad Sci U S A. 2016; 113(13):E1953-62. PMC: 4822637. DOI: 10.1073/pnas.1517935113. View

4.
Chiu W, Chang H, Lin Y, Lin Y, Chang H, Lin H . Bcl2 regulates store-operated Ca entry to modulate ER stress-induced apoptosis. Cell Death Discov. 2018; 4:37. PMC: 5841437. DOI: 10.1038/s41420-018-0039-4. View

5.
Kataoka T, Holler N, Micheau O, Martinon F, Tinel A, Hofmann K . Bcl-rambo, a novel Bcl-2 homologue that induces apoptosis via its unique C-terminal extension. J Biol Chem. 2001; 276(22):19548-54. DOI: 10.1074/jbc.M010520200. View