• 1
    Summers SA, Nelson DH. A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome. Diabetes 2005; 54: 591-602.
  • 2
    Levy M, Futerman AH. Mammalian ceramide synthases. IUBMB Life 2010; 62: 347-356.
  • 3
    Pewzner-Jung Y, Park H, Laviad EL, Silva LC, Lahiri S, Stiban J, et al. A critical role for ceramide synthase 2 in liver homeostasis: I. Alterations in lipid metabolic pathways. J Biol Chem 2010; 285: 10902-10910.
  • 4
    Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH, et al. Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate. J Biol Chem 2008; 283: 5677-5684.
  • 5
    Mizutani Y, Kihara A, Igarashi Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem J 2005; 390: 263-271.
  • 6
    Senkal CE, Ponnusamy S, Bielawski J, Hannun YA, Ogretmen B. Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J 2010; 24: 296-308.
  • 7
    Mesicek J, Lee H, Feldman T, Jiang X, Skobeleva A, Berdyshev EV, et al. Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells. Cell Signal 2010; 22: 1300-1307.
  • 8
    Stratford S, Hoehn KL, Liu F, Summers SA. Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 2004; 279: 36608-36615.
  • 9
    Langeveld M, Aerts JMFG. Glycosphingolipids and insulin resistance. Prog Lipid Res 2009; 48: 196-205.
  • 10
    Gao X, Lowry PR, Zhou X, Depry C, Wei Z, Wong GW, et al. PI3K/Akt signaling requires spatial compartmentalization in plasma membrane microdomains. Proc Natl Acad Sci U S A 2011; 108: 14509-14514.
  • 11
    Tagami S, Inokuchi Ji J-I, Kabayama K, Yoshimura H, Kitamura F, Uemura S, et al. Ganglioside GM3 participates in the pathological conditions of insulin resistance. J Biol Chem 2002; 277: 3085-3092.
  • 12
    Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A, et al. Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 2003; 100: 3445-3449.
  • 13
    Kabayama K, Sato T, Saito K, Loberto N, Prinetti A, Sonnino S, et al. Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance. Proc Natl Acad Sci U S A 2007; 104: 13678-13683.
  • 14
    Pewzner-Jung Y, Brenner O, Braun S, Laviad EL, Ben-Dor S, Feldmesser E, et al. A critical role for ceramide synthase 2 in liver homeostasis: II. Insights into molecular changes leading to hepatopathy. J Biol Chem 2010; 285: 10911-10923.
  • 15
    Kanety H, Hemi R, Papa MZ, Karasik A. Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1. J Biol Chem 1996; 271: 9895-9897.
  • 16
    He Q, Suzuki H, Sharma N, Sharma RP. Ceramide synthase inhibition by fumonisin B1 treatment activates sphingolipid-metabolizing systems in mouse liver. Toxicol Sci 2006; 94: 388-397.
  • 17
    Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1: 31-39.
  • 18
    Vainio S, Heino S, Mansson J-E, Fredman P, Kuismanen E, Vaarala O, et al. Dynamic association of human insulin receptor with lipid rafts in cells lacking caveolae. EMBO Rep 2002; 3: 95-100.
  • 19
    Bickel PE. Lipid rafts and insulin signaling. Am J Physiol Endocrinol Metab 2002; 282: E1-E10.
  • 20
    Bickel PE, Scherer PE, Schnitzer JE, Oh P, Lisanti MP, Lodish HF. Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem 1997; 272: 13793-13802.
  • 21
    Vainio S, Bykov I, Hermansson M, Jokitalo E, Somerharju P, Ikonen E. Defective insulin receptor activation and altered lipid rafts in Niemann-Pick type C disease hepatocytes. Biochem J 2005; 391: 465-472.
  • 22
    Adams JM, Pratipanawatr T, Berria R, Wang E, DeFronzo RA, Sullards MC, et al. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 2004; 53: 25-31.
  • 23
    van de Weijer T, Schrauwen-Hinderling VB, Schrauwen P. Lipotoxicity in type 2 diabetic cardiomyopathy. Cardiovasc Res 2011; 92: 10-18.
  • 24
    Holland WL, Brozinick JT, Wang L-P, Hawkins ED, Sargent KM, Liu Y, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 2007; 5: 167-179.
  • 25
    Ussher JR, Koves TR, Cadete VJJ, Zhang L, Jaswal JS, Swyrd SJ, et al. Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 2010; 59: 2453-2464.
  • 26
    Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. HEPATOLOGY 2005; 42: 987-1000.
  • 27
    Samuel VT, Liu Z-X, Qu X, Elder BD, Bilz S, Befroy D, et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-32353.
  • 28
    Hsieh P-S, Hsieh Y-J. Impact of liver diseases on the development of type 2 diabetes mellitus. World J Gastroenterol 2011; 17: 5240-5245.
  • 29
    Wooten-Blanks LG, Song P, Senkal CE, Ogretmen B. Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1. FASEB J 2007; 21: 3386-3397.
  • 30
    Simons K, Sampaio JL. Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol 2011; 3: a004697.
  • 31
    Iwabuchi K, Nakayama H, Iwahara C, Takamori K. Significance of glycosphingolipid fatty acid chain length on membrane microdomain-mediated signal transduction. FEBS Lett 2010; 584: 1642-1652.
  • 32
    Abrami L, Liu S, Cosson P, Leppla SH, van der Goot FG. Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J Cell Biol 2003; 160: 321-328.
  • 33
    Siddiqui RA, Harvey KA, Zaloga GP, Stillwell W. Modulation of lipid rafts by Omega-3 fatty acids in inflammation and cancer: implications for use of lipids during nutrition support. Nutr Clin Pract 2007; 22: 74-88.
  • 34
    Silva LC, Ben-David O, Pewzner-Jung Y, Laviad EL, Stiban J, Bandyopadhyay S, et al. Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes. J Lipid Res 2012; 53: 430-436.
  • 35
    Iwabuchi K, Prinetti A, Sonnino S, Mauri L, Kobayashi T, Ishii K, et al. Involvement of very long fatty acid-containing lactosylceramide in lactosylceramide-mediated superoxide generation and migration in neutrophils. Glycoconj J 2008; 25: 357-374.
  • 36
    Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 2000; 6: 87-97.
  • 37
    Mochel F, Slama A, Touati G, Desguerre I, Giurgea I, Rabier D, et al. Respiratory chain defects may present only with hypoglycemia. J Clin Endocrinol Metab 2005; 90: 3780-3785.
  • 38
    Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 2012; 13: 225-238.
  • 39
    Cho HY, Gladwell W, Wang X, Chorley B, Bell D, Reddy SP, et al. Nrf2-regulated PPAR expression is critical to protection against acute lung injury in mice. Am J Respir Crit Care Med 2010; 182: 170-182.
  • 40
    Li Y, Xu S, Giles A, Nakamura K, Lee JW, Hou X, et al. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J 2011; 25: 1664-1679.
  • 41
    Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BLG, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331-335.
  • 42
    Zaletel J, Barlovic DP, Prezelj J. Adiponectin-leptin ratio: a useful estimate of insulin resistance in patients with Type 2 diabetes. J Endocrinol Invest 2010; 33: 514-518.