Type 2 diabetes: ceramides as a therapeutic target?

References

• Smyth S, Heron A. Diabetes and obesity: the twin epidemics. Nat. Med. 12, 75–80 (2006).
   Google Scholar
• White JR Jr. Economic considerations in treating patients with Type 2 diabetes mellitus. Am. J. Health Syst. Pharm. 59(Suppl. 9), S14–S17 (2002).
   Google Scholar
• Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia 45, 1201–1210 (2002).
   Google Scholar
• Unger RH. Lipotoxic diseases. Annu. Rev. Med. 53, 319–336 (2002).
   Google Scholar
• Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and Type 2 diabetes. Exp. Clin. Endocrinol. Diabetes 111, 121–124 (2003).
   Google Scholar
• Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 86, 5755–5761 (2001). ▪ Original paper showing an increase in ceramide content in muscle and a lack of correlation between triglyceride content and insulin sensitivity in athletes’ muscles.
   Google Scholar
• Galadari S, Rahman A, Pallichankandy S, Galadari A, Thayyullathil F. Role of ceramide in diabetes mellitus: evidence and mechanisms. Lipids Health Dis. 12, 98 (2013).
   Google Scholar
• Hajduch E, Litherland GJ, Hundal HS. Protein kinase B (PKB/Akt) – a key regulator of glucose transport? FEBS Lett. 492, 199–203 (2001).
   Google Scholar
• Blouin CM, Prado C, Takane KK et al. Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Diabetes 59, 600–610 (2010).
   Google Scholar
• Turban S, Hajduch E. Protein kinase C isoforms: mediators of reactive lipid metabolites in the development of insulin resistance. FEBS Lett. 585, 269–274 (2011).
   Google Scholar
• Haus JM, Kashyap SR, Kasumov T et al. Plasma ceramides are elevated in obese subjects with Type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58, 337–343 (2009). ▪ Complete study showing a correlation beween plasma ceramides and insulin resistance in human.
   Google Scholar
• Coen PM, Dube JJ, Amati F et al. Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59, 80–88 (2010).
   Google Scholar
• Amati F, Dube JJ, Carnero EA et al. Skeletalmuscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes 60(10), 2588–2597 (2011).
   Google Scholar
• Blachnio-Zabielska AU, Koutsari C, Tchkonia T, Jensen MD. Sphingolipid content of human adipose tissue: relationship to adiponectin and insulin resistance. Obesity (Silver Spring) 20(12), 2341–2347 (2012).
   Google Scholar
• Watt MJ, Barnett AC, Bruce CR, Schenk S, Horowitz JF, Hoy AJ. Regulation of plasma ceramide levels with fatty acid oversupply: evidence that the liver detects and secretes de novo synthesised ceramide. Diabetologia 55, 2741–2746 (2012).
   Google Scholar
• Lipina C, Hundal HS. Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance. Diabetologia 54, 1596–1607 (2011). ▪ Excellent review highlighting the importance of ceramides in the progression of insulin resistance.
   Google Scholar
• Reyland ME. Protein kinase C isoforms: multi-functional regulators of cell life and death. Front. Biosci. 14, 2386–2399 (2009).
   Google Scholar
• Mumby M. PP2A: unveiling a reluctant tumor suppressor. Cell 130, 21–24 (2007).
   Google Scholar
• Mullen TD, Hannun YA, Obeid LM. Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem. J. 441, 789–802 (2012). ▪ Good review compiling all data about the role of ceramide synthases.
   Google Scholar
• Veret J, Coant N, Berdyshev EV et al. Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in glucolipotoxicityinduced apoptosis of INS-1 beta-cells. Biochem. J. 438, 177–189 (2011).
   Google Scholar