Deoxysphingolipids: β-Cell, Beware of These New Kids on the Block

  1. Anjaneyulu Kowluru
  1. Beta-Cell Biochemistry Laboratory, John D. Dingell VA Medical Center and Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy, Wayne State University, Detroit, MI
  1. Corresponding author: Anjaneyulu Kowluru, akowluru{at}med.wayne.edu.

Recent estimates by the International Diabetes Federation suggest that the incidence of diabetes soared to an all-time high of 382 million in 2013, compared with 371 million in 2012. The federation predicts that by 2035 the number of individuals afflicted with this disease will increase to 592 million. Furthermore, an alarmingly high number of individuals (∼175 million) is as yet undiagnosed (1). Therefore, efforts to understand the pathophysiology of diabetes are critical for forward movement toward development of novel therapeutic strategies for this disease. Against this backdrop, original investigations by Unger and colleagues (2,3) suggested that chronic exposure and stimulation of the islet β-cell to glucose (glucotoxicity) or free fatty acids (FFAs) (lipotoxicity) result in β-cell dysfunction. Numerous studies using both in vitro and in vivo models have implicated ceramide, a sphingolipid derived from palmitate, in islet dysfunction and death (46). Sphingolipids have also been implicated in the metabolic dysfunction of cells and tissues that are also associated with hypertension and atherosclerosis (7,8).

Recently, Othman et al. (9) reported significantly higher plasma levels of deoxysphingolipids (1-deoxySLs) in patients with metabolic syndrome, suggesting that these atypical sphingolipids might serve as biomarkers for diagnosis and treatment of these patients. It has been shown that mutations in genes encoding specific subunits of serine palmitoyl transferase (SPT), which mediates the de novo biosynthesis of ceramide from palmitoyl CoA and serine, lead to alterations in the …

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  1. doi: 10.2337/db14-0022 Diabetes vol. 63 no. 4 1191-1193
  1. Free via Open Access: OA

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