Toxicity generated through inhibition of pyruvate carboxylase and carnitine palmitoyl transferase-1 is similar to high glucose/palmitate-induced glucolipotoxicity in INS-1 beta cells

Molecular and Cellular Endocrinology

Volumn 383, Issue 1-2, 2014, Pages 48-59

  Lee, Ji Hyun ^a,b   Jung, Ik Rak ^a   Choi, Sung E ^a   Lee, Sung Mi ^a   Lee, Soo Jin ^a   Han, Seung Jin ^a   Kim, Hae Jin ^a   Kim, Dae Jung ^a   Lee, Kwan Woo ^a   Kang, Yup ^a  

^a Ajou University School of Medicine   (South Korea)

^b Korea University   (South Korea)

Author keywords

Anaplerosis; Carnitine palmitoyl transferase 1 (CPT 1); Endoplasmic reticulum (ER) stress; Glucolipotoxicity; INS 1 beta cell; Pyruvate carboxylase (PC)

Indexed keywords

AGENTS AFFECTING LIPID METABOLISM; ANTIOXIDANT; CALCIUM CHANNEL BLOCKING AGENT; CARNITINE PALMITOYLTRANSFERASE I; CASPASE 3; CHAPERONE; ETOMOXIR; GLUCOSE; NITRIC OXIDE SYNTHASE INHIBITOR; OXALOACETIC ACID; PALMITIC ACID; PROTEIN KINASE B; PYRUVATE CARBOXYLASE; REACTIVE OXYGEN METABOLITE; STRESS ACTIVATED PROTEIN KINASE INHIBITOR;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL DEATH; CELL SURVIVAL; CELL VIABILITY; CITRIC ACID CYCLE; CONTROLLED STUDY; CYTOTOXICITY; DIABETES MELLITUS; DNA FRAGMENTATION; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVITY; ENZYME INHIBITION; FATTY ACID OXIDATION; GLUCOLIPOTOXICITY; GLUCOSE OXIDATION; GLUCOSE TRANSPORT; IMMUNOBLOTTING; LIPOTOXICITY; MALE; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; NUTRIENT SUPPLY; OXIDATION; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN CLEAVAGE; RAT; SIGNAL TRANSDUCTION; TRANSMISSION ELECTRON MICROSCOPY;

ANAPLEROSIS; CARNITINE PALMITOYL TRANSFERASE-1 (CPT-1); ENDOPLASMIC RETICULUM (ER) STRESS; GLUCOLIPOTOXICITY; INS-1 BETA CELL; PYRUVATE CARBOXYLASE (PC);

ANIMALS; APOPTOSIS; CALCIUM; CARNITINE O-PALMITOYLTRANSFERASE; CELL LINE, TUMOR; CITRIC ACID CYCLE; ENDOPLASMIC RETICULUM STRESS; EPOXY COMPOUNDS; GENE EXPRESSION REGULATION; GLUCOSE; INSULIN-SECRETING CELLS; MALE; MAP KINASE KINASE 4; MITOCHONDRIA; PALMITIC ACID; PHENYLACETATES; PRIMARY CELL CULTURE; PROTO-ONCOGENE PROTEINS C-AKT; PYRUVATE CARBOXYLASE; RATS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 84891048601     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2013.12.002     Document Type: Article

References (57)

1. Abdul-Ghani M.A., Muller F.L., Liu Y., Chavez A.O., Balas B., Zuo P., Chang Z., Tripathy D., Jani R., Molina-Carrion M., Monroy A., Folli F., Van Remmen H., DeFronzo R.A. Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance. Am. J. Physiol. Endocrinol. Metab. 2008, 295:E678-E685.
2. Akerfeldt M.C., Laybutt D.R. Inhibition of Id1 augments insulin secretion and protects against high-fat diet-induced glucose intolerance. Diabetes 2011, 60:2506-2514.
3. Bachar E., Ariav Y., Ketzinel-Gilad M., Cerasi E., Kaiser N., Leibowitz G. Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic beta-cells via activation of mTORC1. PLoS ONE 2009, 4:e4954.
4. Beal M.F. Energetics in the pathogenesis of neurodegenerative disease. Trends, Neurosci. 2000, 23:298-304.
5. Bonnard C., Durand A., Peyrol S., Chanseaume E., Chauvin M.A., Morio B., Vidal H., Rieusset J. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J. Clin. Invest. 2008, 118:789-800.
6. Busch A.K., Cordery D., Denyer G.S., Biden T.J. Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic beta-cell function. Diabetes 2002, 51:977-987.
7. Choe S.S., Choi A.H., Lee J.W., Kim K.H., Chung J.J., Park J., Lee K.M., Park K.G., Lee I.K., Kim J.B. Chronic activation of liver X receptor induces beta-cell apoptosis through hyperactivation of lipogenesis: liver X receptor-mediated lipotoxicity in pancreatic beta-cells. Diabetes 2007, 56:1534-1543.
8. 2+-mediated apoptotic signals in palmitate-induced MIN6N8a beta cell death. Mol. Cell. Endocrinol. 2007, 272:50-62.
9. Choi S.E., Jung I.R., Lee Y.J., Lee S.J., Lee J.H., Kim Y., Jun H.S., Lee K.W., Park C.B., Kang Y. Stimulation of lipogenesis as well as fatty acid oxidation protects against palmitate-induced INS-1 beta-cell death. Endocrinology 2011, 152:816-827.
10. Choi S.E., Lee Y.J., Hwang G.S., Chung J.H., Lee S.J., Lee J.H., Han S.J., Kim H.J., Lee K.W., Kim Y., Jun H.S., Kang Y. Supplement of TCA cycle intermediates protects against high glucose/palmitate-induced INS-1 beta cell death. Arch. Biochem. Biophys. 2011, 505:231-241.
11. Ciapaite J., Bakker S.J., van Diamant M., Eikenhorst G., Heine R.J., Westerhoff H.V., Krab K. Metabolic control of mitochondrial properties by adenine nucleotide translocator determines palmitoyl-CoA effects. Implications for a mechanism linking obesity and type 2 diabetes. FEBS. J. 2006, 273:5288-5302.
12. Cnop M., Hannaert J.C., Hoorens A., Eizirik D.L., Pipeleers D.G. Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 2001, 50:1771-1777.
13. Cunha D.A., Hekerman P., Ladriere L., Bazarra-Castro A., Ortis F., Wakeham M.C., Moore F., Rasschaert J., Cardozo A.K., Bellomo E., Overbergh L., Mathieu C., Lupi R., Hai T., Herchuelz A., Marchetti P., Rutter G.A., Eizirik D.L., Cnop M. Initiation and execution of lipotoxic ER stress in pancreatic beta-cells. J. Cell. Sci. 2008, 121:2308-2318.
14. Eitel K., Staiger H., Rieger J., Mischak H., Brandhorst H., Brendel M.D., Bretzel R.G., Häring H.U., Kellerer M. Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells. Diabetes 2003, 52:991-997.
15. El-Assaad W., Buteau J., Peyot M.L., Nolan C., Roduit R., Hardy S., Joly E., Dbaibo G., Rosenberg L., Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology 2003, 144:4154-4163.
16. El-Assaad W., Joly E., Barbeau A., Sladek R., Buteau J., Maestre I., Pepin E., Zhao S., Iglesias J., Roche E., Prentki M. Glucolipotoxicity alters lipid partitioning and causes mitochondrial dysfunction, cholesterol, and ceramide deposition and reactive oxygen species production in INS832/13 ss-cells. Endocrinology 2010, 151:3061-3073.
17. Green C.D., Olson L.K. Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6. Am. J. Physiol. Endocrinol. Metab. 2011, 300:E640-649.
18. Greten F.R., Weber C.K., Greten T.F., Schneider G., Wagner M., Adler G., Schmid R.M. Stat3 and NF-kB activation prevents apoptosis in pancreatic carcinogenesis. Gastroenterology 2002, 123:2052-2063.
19. 2+ homeostasis in beta cells. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E690-E701.
20. Han S.J., Choi S.E., Yi S.A., Lee S.J., Kim H.J., Kim D.J., Lee H.C., Lee K.W., Kang Y. β-cell-protective effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) as a glutamate dehydrogenase (GDH) activator in db/db mice. J. Endocrinol. 2012, 212:307-315.
21. Hennige A.M., Ranta F., Heinzelmann I., Düfer M., Michael D., Braumüller H., Lutz S.Z., Lammers R., Drews G., Bosch F., Häring H.U., Ullrich S. Overexpression of kinase-negative protein kinase Cdelta in pancreatic beta-cells protects mice from diet-induced glucose intolerance and beta-cell dysfunction. Diabetes 2010, 59:119-127.
22. Higa M., Shimabukuro M., Shimajiri Y., Takasu N., Shinjyo T., Inaba T. Protein kinase B/Akt signalling is required for palmitate-induced beta-cell lipotoxicity. Diabetes. Obes. Metab. 2006, 8:228-233.
23. Hirabara S.M., Curi R., Maechler P. Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. J. Cell. Physiol. 2010, 222:187-194.
24. Karaskov E., Scott C., Zhang L., Teodoro T., Ravazzola M., Volchuk A. Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology 2006, 147:3398-3407.
25. Koves T.R., Ussher J.R., Noland R.C., Slentz D., Mosedale M., Ilkayeva O., Bain J., Stevens R., Dyck J.R., Newgard C.B., Lopaschuk G.D., Muoio D.M. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008, 7:45-56.
26. Kwon J.I., Kim G.Y., Park K.Y., Ryu C.H., Choi Y.H. Induction of apoptosis by linoleic acid is associated with the modulation of Bcl-2 family and Fas/FasL system and activation of caspases in AGS human gastric adenocarcinoma cells. J. Med. Food 2008, 11:1-8.
27. Lai E., Bikopoulos G., Wheeler M.B., Rozakis-Adcock M., Volchuk A. Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic beta-cells. Am. J. Physiol. Endocrinol. Metab. 2008, 294:E540-E550.
28. Landau Z., Forti E., Alcaly M., Birk R.Z. Palmitate induced lipoapoptosis of exocrine pancreas AR42J cells. Apoptosis 2006, 11:717-724.
29. Lee S.M., Choi S.E., Lee J.H., Lee J.J., Jung I.R., Lee S.J., Lee K.W., Kang Y. Involvement of the TLR4 (Toll-like receptor4) signaling pathway in palmitate-induced INS-1 beta cell death. Mol. Cell. Biochem. 2011, 354:207-217.
30. Lee S.J., Choi S.E., Jung I.R., Lee K.W., Kang Y. Protective effect of nicotinamide on high glucose/palmitate-induced glucolipotoxicity to INS-1 beta cells is attributed to its inhibitory activity to sirtuins. Arch. Biochem. Biophys. 2013, 535:187-196.
31. Lin N., Chen H., Zhang H., Wan X., Su Q. Mitochondrial reactive oxygen species (ROS) inhibition ameliorates palmitate-induced INS-1 beta cell death. Endocrine. 2012, 42:107-117.
32. Lingohr M.K., Dickson L.M., Wrede C.E., Briaud I., McCuaig J.F., Myers M.G., Rhodes C.J. Decreasing IRS-2 expression in pancreatic beta-cells (INS-1) promotes apoptosis, which can be compensated for by introduction of IRS-4 expression. Mol. Cell. Endocrinol. 2003, 209:17-31.
33. Listenberger L.L., Han X., Lewis S.E., Cases S., Farese R.V., Ory D.S., Schaffer J.E. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. USA 2003, 100:3077-3082.
34. Lu H., Koshkin V., Allister E.M., Gyulkhandanyan A.V., Wheeler M.B. Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes. Diabetes 2010, 59:448-459.
35. Lupi R., Dotta F., Marselli L., Del Guerra S., Masini M., Santangelo C., Patané G., Boggi U., Piro S., Anello M., Bergamini E., Mosca F., Di Mario U., Del Prato S., Marchetti P. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 2002, 51:1437-1442.
36. MacDonald M.J., Fahien L.A., Brown L.J., Hasan N.M., Buss J.D., Kendrick M.A. Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. Am. J. Physiol. Endocrinol. Metab. 2005, 288:E1-E15.
37. MacDonald M.J., Longacre M.J., Langberg E.C., Tibell A., Kendrick M.A., Fukao T., Ostenson C.G. Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes. Diabetologia 2009, 52:1087-1091.
38. Nabben M., Hoeks J., Briede J.J., Glatz J.F., Moonen-Kornips E., Hesselink M.K., Schrauwen P. The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice. FEBS. Lett. 2008, 582:4147-4152.
39. Okuyama R., Fujiwara T., Ohsumi J. High glucose potentiates palmitate-induced NO-mediated cytotoxicity through generation of superoxide in clonal beta-cell HIT-T15. FEBS Lett. 2003, 545:219-223.
40. Piro S., Anello M., Di Pietro C., Lizzio M.N., Patanè G., Rabuazzo A.M., Vigneri R., Purrello M., Purrello F. Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: possible role of oxidative stress. Metabolism 2002, 51:1340-1347.
41. Poitout V., Robertson R.P. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr. Rev. 2008, 29:351-366.
42. Prentki M., Joly E., El-Assaad W., Roduit R. Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes 2002, 51(Suppl. 3):s405-s413.
43. Prentki M., Madiraju S.R. Glycerolipid/free fatty acid cycle and islet β-cell function in health, obesity and diabetes. Mol. Cell. Endocrinol. 2011, 353(1-2):88-100.
44. Radad K., Rausch W.D., Gille G. Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochem. Int. 2006, 49:379-386.
45. Robertson R., Zhou H., Zhang T., Harmon J.S. Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell. Biochem. Biophys. 2007, 48:139-146.
46. Ruderman N., Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat. Rev. Drug. Discov. 2004, 3:340-351.
47. Sargsyan E., Bergsten P. Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells. Lipids Health Dis. 2011, 10:115.
48. Sol E.M., Sargsyan E., Akusjärvi G., Bergsten P. Glucolipotoxicity in INS-1E cells is counteracted by carnitine palmitoyltransferase 1 over-expression. Biochem. Biophys. Res. Commun. 2008, 375:517-521.
49. Summermatter S., Shui G., Maag D., Santos G., Wenk M.R., Handschin C. PGC-1α improves glucose homeostasis in skeletal muscle in an activity-dependent manner. Diabetes 2013, 62:85-95.
50. Szegezdi E., E Logue S.E., Gorman A.M., Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO. Rep. 2006, 7:880-885.
51. Wang X., Zhou L., Li G., Luo T., Gu Y., Qian L., Fu X., Li F., Li J., Luo M. Palmitate activates AMP-activated protein kinase and regulates insulin secretion from beta cells. Biochem. Biophys. Res. Commun. 2007, 352:463-468.
52. Wang W., Liu Y., Chen Y., Cao C., Xiang Y., Zhang D., Han L., Zhao H., Liu G. Inhibition of Foxo1 mediates protective effects of ghrelin against lipotoxicity in MIN6 pancreatic beta-cells. Peptides 2010, 31:307-314.
53. Watt M.J., Steinberg G.R., Chen Z.P., Kemp B.E., Febbraio M.A. Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes. J. Physiol. 2006, 574:139-147.
54. Wochna A., Niemczyk E., Kurono C., Masaoka M., Kedzior J., Słomińska E., Lipiński M., Wakabayashi T. Possible role of oxidative stress in the switch mechanism of the cell death mode from apoptosis to necrosis-studies on rho0 cells. Mitochondrion 2007, 7:119-124.
55. Woldegiorgis G., Yousufzai S.Y., Shrago E. Studies on the interaction of palmitoyl coenzyme a with the adenine nucleotide translocase. J. Biol. Chem. 1982, 257:14783-14787.
56. Weigle D.S., Selfridge L.E., Schwartz M.W., Seeley R.J., Cummings D.E., Havel P.J., Kuijper J.L., BeltrandelRio H. Elevated free fatty acids induce uncoupling protein 3 expression in muscle. A potential explanation for the effect of fasting. Diabetes 1998, 47:298-302.
57. Xu J., Han J., Epstein P.N., Liu Y.Q. Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets. Biochem. Biophys. Res. Commun. 2006, 344:827-833.