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.
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http://dx.doi.org/10.3390/biomedicines13010223 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760435 | PMC |
Biomedicines
January 2025
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández de Elche, 03202 Elche, Alicante, Spain.
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.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Introduction: Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer to treat. While previous studies have demonstrated that ginsenoside Rh2 induces apoptosis in TNBC cells, the specific molecular targets and underlying mechanisms remain poorly understood. This study aims to uncover the molecular mechanisms through which ginsenoside Rh2 regulates apoptosis and proliferation in TNBC, offering new insights into its therapeutic potential.
View Article and Find Full Text PDFJ Biol Methods
December 2024
National Center for Scientific Research UMR 8003, Paris City University, SSPIN Neuroscience Institute, Saint-Germain Campus, Paris, Île de France 75006, France.
Background: HA14-1 is a small-molecule, stable B-cell lymphoma 2 (Bcl-2) antagonist that promotes apoptosis in malignant cells through an incompletely-defined mechanism of action. Bcl-2 and related anti-apoptotic proteins, such as B-cell lymphoma-extra-large [Bcl-XL]), are predominantly localized to the outer mitochondrial membrane, where they regulate cell death pathways. However, the notably short half-life of HA14-1 limits its potential therapeutic application.
View Article and Find Full Text PDFIran J Pharm Res
May 2024
Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear.
View Article and Find Full Text PDFAdv Clin Exp Med
January 2025
Department of Neurosurgery, The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an Children's Hospital, China.
Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor malignancy in adults, accounting for nearly 50% of all gliomas. Current medications for GBM frequently lead to drug resistance.
Objectives: Umbelliferone (UMB) is found extensively in many plants and shows numerous pharmacological actions against inflammation, degenerative diseases and cancers.
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