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Open AccessReview

Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by Lipotoxicity

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
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2014, 3(2), 646-662; https://doi.org/10.3390/jcm3020646
Received: 5 March 2014 / Revised: 10 April 2014 / Accepted: 11 April 2014 / Published: 20 June 2014
(This article belongs to the Special Issue Obesity, Diabetes and Metabolic Syndrome)
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
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Véret, J.; Bellini, L.; Giussani, P.; Ng, C.; Magnan, C.; Stunff, H.L. Roles of Sphingolipid Metabolism in Pancreatic β Cell Dysfunction Induced by Lipotoxicity. J. Clin. Med. 2014, 3, 646-662.

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