Inhibiting glycosphingolipid synthesis improves glycemic control and insulin sensitivity in animal models of type 2 diabetes

Diabetes

Volumn 56, Issue 5, 2007, Pages 1210-1218

  Zhao, Hongmei ^a   Przybylska, Malgorzata ^a   Wu, I Huan ^a   Zhang, Jinhua ^a   Siegel, Craig ^a   Komarnitsky, Svetlana ^a   Yew, Nelson S ^a,b   Cheng, Seng H ^a,b  

^a Genzyme   (United States)

^b GENZYME CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CERAMIDE GLUCOSYLTRANSFERASE INHIBITOR; CHOLESTEROL; GANGLIOSIDE GM3; GENZ 123346; GLUCOSE; GLUCOSYLCERAMIDE; GLYCOSPHINGOLIPID; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN; INSULIN RECEPTOR; MIGLUSTAT; NONANOIC ACID[2 (2',3' DIHYDROBENZO[1,4]DIOXIN 6' YL) 2 HYDROXYL 1 PYRROLIDIN 1 YLMETHYLETHYL]AMIDE LEVO TARTARIC ACID; PLACEBO; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL FUNCTION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DOSE REDUCTION; DRUG HALF LIFE; DRUG MECHANISM; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; GLYCEMIC CONTROL; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN SENSITIVITY; LIPID BLOOD LEVEL; LIPID DIET; LIPOGENESIS; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT; WEIGHT REDUCTION; ZUCKER DIABETIC FATTY RAT;

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DIOXANES; DISEASE MODELS, ANIMAL; GLUCOSYLCERAMIDES; GLYCOSPHINGOLIPIDS; HEMOGLOBIN A, GLYCOSYLATED; HYPOGLYCEMIC AGENTS; INSULIN; LIPIDS; LIVER; MALE; OBESITY; PYRROLIDINES; RATS; RATS, ZUCKER;

EID: 34248228704     PISSN: 00121797     EISSN: 00121797     Source Type: Journal    
DOI: 10.2337/db06-0719     Document Type: Article

References (32)

1. Saltiel AR, Kahn CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799-806, 2001
2. Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 365:1415-1428, 2005
3. Perseghin G, Petersen K, Shulman GI: Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 27 (Suppl. 3):S6 -S11, 2003
4. Hegarty BD, Furler SM, Ye J, Cooney GJ, Kraegen EW: The role of intramuscular lipid in insulin resistance. Acta Physiol Scand 178:373-383, 2003
5. Allende ML, Proia RL: Lubricating cell signaling pathways with gangliosides. Curr Opin Struct Biol 12:587-592, 2002
6. Bremer EG, Schlessinger J, Hakomori S: Ganglioside-mediated modulation of cell growth: specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J Biol Chem 261:2434 -2440, 1986
7. Liu Y, Li R, Ladisch S: Exogenous ganglioside GD1a enhances epidermal growth factor receptor binding and dimerization. J Biol Chem 279:36481-36489, 2004
8. Nishio M, Tajima O, Furukawa K, Urano T: Over-expression of GM1 enhances cell proliferation with epidermal growth factor without affecting the receptor localization in the microdomain in PC12 cells. Int J Oncol 26:191-199, 2005
9. Mitsuda T, Furukawa K, Fukumoto S, Miyazaki H, Urano T: Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals. J Biol Chem 277:11239-11246, 2002
10. Pike LJ: Lipid rafts: bringing order to chaos. J Lipid Res 44:655-667, 2003
11. Ikonen E, Vainio S: Lipid microdomains and insulin resistance: is there a connection? Sci STKE 2005:pe3, 2005
12. Tagami S, Inokuchi Ji J, Kabayama K, Yoshimura H, Kitamura F, Uemura S, Ogawa C, Ishii A, Saito M, Ohtsuka Y, Sakaue S, Igarashi Y: Ganglioside GM3 participates in the pathological conditions of insulin resistance. J Biol Chem 277:3085-3092, 2002
13. Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A, Kono M, Tsuji S, Daniotti JL, Werth N, Sandhoff R, Sandhoff K, Proia RL: Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 100:3445-3449, 2003
14. Miller SP, Zirzow GC, Doppelt SH, Brady RO, Barton NW: Analysis of the lipids of normal and Gaucher bone marrow. J Lab Clin Med 127:353-358, 1996
15. Abe A, Arend LJ, Lee L, Lingwood C, Brady RO, Shayman JA: Glycosphingolipid depletion in fabry disease lymphoblasts with potent inhibitors of glucosylceramide synthase. Kidney Int 57:446-454, 2000
16. Ames BN: Assay of inorganic phosphate, total phosphate and phosphatases. In Methods in Enzymology. Colowick SP, Kaplan NO, Eds. New York, Academic Press, 1966, p. 115-118
17. Kolter T, Proia RL, Sandhoff K: Combinatorial ganglioside biosynthesis. J Biol Chem 277:25859-25862, 2002
18. Lee L, Abe A, Shayman JA: Improved inhibitors of glucosylceramide synthase. J Biol Chem 274:14662-14669, 1999
19. Shayman JA, Lee L, Abe A, Shu L: Inhibitors of glucosylceramide synthase. Methods Enzymol 311:373-387, 2000
20. Platt FM, Neises GR, Karlsson GB, Dwek RA, Butters TD: N-butyldeoxygalactonojirimycin inhibits glycolipid biosynthesis but does not affect N-linked oligosaccharide processing. J Biol Chem 269:27108-27114, 1994
21. Butters TD, Dwek RA, Platt FM: Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses. Glycobiology 15:43R-52R, 2005
22. Clark JB, Palmer CJ, Shaw WN: The diabetic Zucker fatty rat. Proc Soc Exp Biol Med 173:68-75, 1983
23. Nojiri H, Stroud M, Hakomori S: A specific type of ganglioside as a modulator of insulin-dependent cell growth and insulin receptor tyrosine kinase activity: possible association of ganglioside-induced inhibition of insulin receptor function and monocytic differentiation induction in HL-60 cells. J Biol Chem 266:4531-4537, 1991
24. Sasaki A, Hata K, Suzuki S, Sawada M, Wada T, Yamaguchi K, Obinata M, Tateno H, Suzuki H, Miyagi T: Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice. J Biol Chem 278:27896-27902, 2003
25. Saltiel AR, Pessin JE: Insulin signaling in microdomains of the plasma membrane. Traffic 4:711-716, 2003
26. Vainio S, Heino S, Mansson JE, Fredman P, Kuismanen E, Vaarala O, Ikonen E: Dynamic association of human insulin receptor with lipid rafts in cells lacking caveolae. EMBO Rep 3:95-100, 2002
27. Kabayama K, Sato T, Kitamura F, Uemura S, Kang BW, Igarashi Y, Inokuchi J: TNFalpha-induced insulin resistance in adipocytes as a membrane microdomain disorder: involvement of ganglioside GM3. Glycobiology 15:21-29, 2005
28. Chavez JA, Knotts TA, Wang LP, Li G, Dobrowsky RT, Florant GL, Summers SA: A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 278:10297-10303, 2003
29. Summers SA, Garza LA, Zhou H, Birnbaum MJ: Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol Cell Biol 18:5457-5464, 1998
30. 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 54:591-602, 2005
31. Unger RH: Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144:5159-5165, 2003
32. Shimabukuro M, Higa M, Zhou YT, Wang MY, Newgard CB, Unger RH: Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats: role of serine palmitoyltransferase overexpression. J Biol Chem 273:32487-32490, 1998