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

Journal of Clinical Medicine

Julien Véret¹  Lara Bellini¹  Paola Giussani²  Carl Ng³  Christophe Magnan¹ 

[1] University Paris Diderot, Sorbonne Paris City, Unit of Functional and Adaptative Biology UMR 8251 CNRS, 75205 Paris Cedex 13, France; E-Mails:;Department of Medical Biotechnology and Translational Medicine, University of Milan, LITA Segrate, Via Fratelli Cervi 93, 20090 Segrate (MI), Italy; E-Mail:;School of Biology and Environmental Science and UCD Earth Institute, University College Dublin, Belfield, Dublin 4, Ireland; E-Mail:

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

DOI  :  10.3390/jcm3020646

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.