Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by LipotoxicityReportar como inadecuado




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1

University Paris Diderot, Sorbonne Paris City, Unit of Functional and Adaptative Biology UMR 8251 CNRS, 75205 Paris Cedex 13, France

2

Department of Medical Biotechnology and Translational Medicine, University of Milan, LITA Segrate, Via Fratelli Cervi 93, 20090 Segrate MI, Italy

3

School of Biology and Environmental Science and UCD Earth Institute, University College Dublin, Belfield, Dublin 4, Ireland



These authors contributed equally to this work.





*

Author to whom correspondence should be addressed.



Abstract Pancreatic β cells secrete insulin in order to maintain glucose homeostasis. However, various environmental stresses such as obesity have been shown to induce loss of secretory responsiveness in pancreatic β cells and pancreatic β cell apoptosis which can favor the development of type 2 diabetes T2D. Indeed, elevated levels of free fatty acids FFAs have been shown to induce β cell apoptosis. Importantly, the chronic adverse effects of FFAs on β cell function and viability are potentiated in the presence of hyperglycaemia, a phenomenon that has been termed gluco-lipotoxicity. The molecular mechanisms underlying the pathogenesis of gluco-lipotoxicity in pancreatic β cells are not completely understood. Recent studies have shown that sphingolipid metabolism plays a key role in gluco-lipotoxicity induced apoptosis and loss of function of pancreatic β cells. The present review focuses on how the two main sphingolipid mediators, ceramides and sphingoid base-1-phosphates, regulate the deleterious effects of gluco-lipotoxicity on pancreatic β cells. The review highlights the role of a sphingolipid biostat on the dysregulation of β cell fate and function induced by gluco-lipotoxicity, offering the possibility of new therapeutic targets to prevent the onset of T2D. View Full-Text

Keywords: obesity; type 2 diabetes; gluco-lipotoxicity; islet of Langherans; ceramide; sphingosine-1-phosphate; sphingolipids; apoptosis; insulin; pancreas obesity; type 2 diabetes; gluco-lipotoxicity; islet of Langherans; ceramide; sphingosine-1-phosphate; sphingolipids; apoptosis; insulin; pancreas





Autor: Julien Véret 1,†, Lara Bellini 1,†, Paola Giussani 2, Carl Ng 3, Christophe Magnan 1 and Hervé Le Stunff 1,*

Fuente: http://mdpi.com/



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