Diabetes Research and Clinical Practice
Volume 56, Issue 2 , Pages 83-92 , May 2002

Troglitazone ameliorates lipotoxicity in the beta cell line INS-1 expressing PPAR gamma

  • Toshihide Kawai

      Affiliations

    • Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • ,
  • Hiroshi Hirose

      Affiliations

    • Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81-3-3353-1211; fax: +81-3-5269-3219
    • ,
  • Yoshiko Seto

      Affiliations

    • Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • ,
  • Haruhisa Fujita

      Affiliations

    • Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • ,
  • Hiroshi Fujita

      Affiliations

    • Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • ,
  • Kaname Ukeda

      Affiliations

    • Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
    • ,
  • Takao Saruta

      Affiliations

    • Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Received 25 February 2001 ,Revised 14 September 2001 ,Accepted 9 November 2001.

References 

  1. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79:1147–1156
  2. Lehmann JM, Moore RB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. 1995;270:12953–12956
  3. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-Deoxy-Δ12,14 prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995;83:803–812
  4. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell. 1995;83:813–819
  5. Tontonoz P, Singer S, Forman BM, et al.  Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc. Natl. Acad. Sci. USA. 1997;94:237–241
  6. Demetri GD, Fletcher CDM, Mueller E, et al.  Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA. 1999;96:3951–3956
  7. Mueller E, Sarraf P, Tontonoz P, et al.  Terminal differentiation of human breast cancer through PPAR gamma. Mol. Cell. 1998;1:465–470
  8. Sarraf P, Mueller E, Jones D, et al.  Differentiation and reversal of malignant changes in colon cancer through PPAR gamma. Nat. Med. 1998;4:1046–1052
  9. Lefebvre A-M, Chen I, Desreumaux P, et al.  Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat. Med. 1998;4:1053–1057
  10. Saez E, Tontonoz P, Nelson MC, et al.  Activators of the nuclear receptor PPAR gamma enhance colon polyp formation. Nat. Med. 1998;4:1058–1061
  11. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–514
  12. Okuno A, Tamemoto H, Tobe K, et al.  Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Invest. 1998;101:1354–1361
  13. Kawai T, Takei I, Oguma Y, et al.  Effects of troglitazone on fat distribution in the treatment of male type 2 diabetes. Metabolism. 1999;48:1102–1107
  14. Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral anti-diabetic agent CS-045; studies in KK and ob/ob mice and Zucker fatty rats. Diabetes. 1988;37:1549–1558
  15. Mimura K, Umeda F, Hiramatsu S, et al.  Effects of a new oral hypoglycemic agent (CS-045) on metabolic abnormalities and insulin resistance in type 2 diabetes. Diabetic Med. 1994;11:685–691
  16. Suter SL, Nolan JJ, Wallace P, Gumbiner B, Olefsky JM. Metabolic effects of new oral hypoglycemic agent troglitazone in NIDDM subjects. Diabetes Care. 1992;15:193–203
  17. Masuda K, Okamoto Y, Tsuura Y, et al.  Effects of troglitazone (CS-045) on insulin secretion in isolated rat pancreatic islets and HIT cells: an insulinotropic mechanism distinct from glibenclamide. Diabetologia. 1995;38:24–30
  18. Ohtani K, Shimizu H, Tanaka Y, Sato N, Mori M. Pioglitazone hydrochloride stimulates insulin secretion in HIT-T 15 cells by inducing Ca2+ influx. J. Endocrinol. 1996;150:107–111
  19. Ohtani K, Shimizu H, Sato N, Mori M. Troglitazone (CS-045) inhibits ß-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells. Endocrinology. 1998;139:172–178
  20. Fujiwara T, Wada M, Fukuda K, et al.  Characterization of CS-045, a new oral antidiabetic agent, II. Effects on glycemic control and pancreatic islet structure at a late stage of the diabetic syndrome in C57BL/KsJ-db/db mice. Metabolism. 1991;40:1213–1218
  21. Cavaghan MK, Ehrmann DA, Byrne MM, Polonsky KS. Treatment with the oral antidiabetic agent troglitazone improves ß cell responses to glucose in subjects with impaired glucose tolerance. J. Clin. Invest. 1997;100:530–537
  22. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH. cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte–ß-cell relationships. Proc. Natl. Acad. Sci. USA. 1994;91:10878–10882
  23. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Diabetes. 1995;44:863–870
  24. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 1997;46:3–10
  25. McGarry JD, Dobbins RL. Fatty acids, lipotoxicity and insulin secretion. Diabetologia. 1999;42:128–138
  26. Stein DT, Stevenson BE, Chester MW, et al.  The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J. Clin. Invest. 1997;100:398–403
  27. Komatsu M, Sharp GWG. Palmitate and myristate selectively mimic the effect of glucose in augmenting insulin release in the absence of extracellular Ca2+. Diabetes. 1998;47:352–357
  28. Kawai T, Hirose H, Seto Y, Fujita H, Saruta T. Chronic effects of different fatty acids and leptin in INS-1 cells. Diabetes Res. Clin. Pract. 2001;51:1–8
  29. Asfari M, Janjic D, Meda P, Li G, Halban PA, Wollheim CB. Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology. 1992;130:167–178
  30. Tanaka T, Itoh H, Doi K, et al.  Down regulation of peroxisome proliferator-activated receptor gamma expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia. 1999;42:702–710
  31. Janjic D, Wollheim CB. Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay. Diabetologia. 1992;35:482–485
  32. Kliewer SA, Sundseth SS, Jones SA, et al.  Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA. 1997;94:4318–4323
  33. Inoue Y, Tanigawa K, Nakamura S, et al.  Lack of effect of CS-045, a new antidiabetic agent, on insulin secretion in the remnant pancreas after 90% pancreatectomy in rats. Diabetes Res. Clin. Pract. 1995;27:19–26
  34. Prigeon RL, Kahn SE, Porte D. Effect of troglitazone on B cell function, insulin sensitivity, and glycemic control in subjects with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 1998;83:819–823
  35. Shimabukuro M, Zhou Y-T, Lee Y, Unger RH. Troglitazone lowers islet fat and restores beta cell function of Zucker diabetic fatty rats. J. Biol. Chem. 1998;273:3547–3550
  36. Wang M, Wise SC, Leff T, Su T-Z. Troglitazone, an antidiabetic agent, inhibits cholesterol biosynthesis through a mechanism independent of peroxisome proliferator-activated receptor-gamma. Diabetes. 1999;48:254–260
  37. Cook DL, Hales CN. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature. 1984;311:271–273
  38. Ashcroft FM, Harrison DE, Ashcroft SJH. Glucose induces closure of single potassium channels in isolated rat pancreatic ß-cells. Nature. 1984;312:446–448
  39. Sato Y, Aizawa T, Komatsu M, Okada N, Yamada T. Dual functional role of membrane depolarization/Ca2+ influx in rat pancreatic ß-cell. Diabetes. 1992;41:438–443
  40. Komatsu M, Schermerhorn T, Noda M, Straub SG, Aizawa T, Sharp GWG. Augmentation of insulin release by glucose in the absence of extracellular Ca2+. Diabetes. 1997;46:1928–1938
  41. Komatsu M, Schermerhorn T, Aizawa T, Sharp GWG. Glucose stimulation of insulin release in the absence of extracellular Ca2+ and in the absence of any rise in intracellular Ca2+ in rat pancreatic islets. Proc. Natl. Acad. Sci. USA. 1995;92:10728–10732
  42. Eto K, Tsubamoto Y, Terauchi Y, et al.  Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science. 1999;283:981–985
  43. Sunaga Y, Inagaki N, Gonoi T, et al.  Troglitazone but not pioglitazone affects ATP-sensitive K(+) channel activity. Eur. J. Pharmacol. 1999;381:71–76
  44. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92:829–839
  45. Sato Y, Henquin JC. The K+-ATP channel-independent pathway of regulation of insulin secretion by glucose. Diabetes. 1998;47:1713–1721

☆ The content of this paper has been presented at the 42nd Annual Meeting of the Japan Diabetes Society (13–15 May 1999, Yokohama).

PII: S0168-8227(01)00367-9

Diabetes Research and Clinical Practice
Volume 56, Issue 2 , Pages 83-92 , May 2002

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