Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
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http://dx.doi.org/10.1016/j.bmcl.2015.08.022 | DOI Listing |
Metabolism
January 2025
Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA, USA. Electronic address:
Introduction: Type 1 diabetic human islet β-cells are deficient in double C 2 like domain beta (DOC2b) protein. Further, DOC2b protects against cytokine-induced pancreatic islet β-cell stress and apoptosis. However, the mechanisms underpinning the protective effects of DOC2b remain unknown.
View Article and Find Full Text PDFSci Rep
January 2025
MARBIO, UiT - The Arctic University of Norway, Breivika, 9037, Tromsø, Norway.
Pro-inflammatory cytokines, like interleukin-1 beta and interferon gamma, are known to activate signalling pathways causing pancreatic beta cell death and dysfunction, contributing to the onset of diabetes. Targeting cytokine signalling pathways offers a potential strategy to slow or even halt disease progression, reducing reliance on exogenous insulin and improving glucose regulation. This study explores the protective and proliferative effects of breitfussin C (BfC), a natural compound isolated from the Arctic marine hydrozoan Thuiaria breitfussi, on pancreatic beta cells exposed to pro-inflammatory cytokines.
View Article and Find Full Text PDFViruses
November 2024
Department of Microbiology & Immunology, Stanford Medical School, Stanford University, Stanford, CA 94305, USA.
Cytomegaloviruses, species-specific members of the betaherpesviruses, encode an impressive array of immune evasion strategies committed to the manipulation of the host immune system enabling these viruses to remain for life in a stand-off with host innate and adaptive immune mechanisms. Even though they are species-restricted, cytomegaloviruses are distributed across a wide range of different mammalian species in which they cause systemic infection involving many different cell types. Regulated, or programmed cell death has a recognized potential to eliminate infected cells prior to completion of viral replication and release of progeny.
View Article and Find Full Text PDFBiomolecules
November 2024
Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancreatic beta-cell function, as well as on glucose tolerance and appetite.
View Article and Find Full Text PDFIntroduction: Type 1 diabetic human islet β-cells are deficient in double C 2 like domain beta (DOC2b) protein. Further, DOC2b protects against cytokine-induced pancreatic islet β-cell stress and apoptosis. However, the mechanisms underpinning the protective effects of DOC2b remain unknown.
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