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J. Clin. Med. 2014, 3(2), 646-662; doi:10.3390/jcm3020646
Review

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

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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)
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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.
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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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