Skip to main content
Log in

Pleiotropic effects of thiazolidinediones: Taking a look beyond antidiabetic activity

  • Review Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Thiazolidinediones (TZD) [Troglitazone (TRO), Pioglitazone (PGZ), Rosiglitazone, (RGZ)] are a novel class of antidiabetic drugs for patients with Type-2 diabetes mellitus (T2DM) able to decrease blood glucose, working through a reduction of insulin resistance. The family of TZD exerts its effect specifically bound to peroxisome proliferator- activated receptor ψ (PPARψ). This is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, together with PPARa and dgB. Although PPARψ is essentially expressed in adipose tissue, it has also been found in endothelial cells, macrophages, vascular smooth muscle cells, glomerular mesangial cells, hepatic stellate cells and in several cancer cell lines. In these cells, the PPARψ activation by TZD determines modulatory effects on growth factor release, production of cytokine, cell proliferation and migration, extracellular matrix remodeling and control on cell cycle progression and differentiation. In addition, TZD have been shown to have a potent antioxidant effect. This review, taking a quick look beyond the antidiabetic activity of PPARψ, shows the dramatic ranging of medical implications that the use of TZD could have modulating the PPARψ activity in several diseases with a strong social impact, such as insulin resistance syndrome, chronic inflammation, atherosclerosis and cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999, 20: 649–88.

    PubMed  CAS  Google Scholar 

  2. Fujiwara T, Horikoshi H. Troglitazone and related compounds therapeutic potential beyond diabetes. Life Sci 2000, 67: 2405–16.

    Article  PubMed  CAS  Google Scholar 

  3. Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 1994, 331: 1188–93.

    Article  PubMed  CAS  Google Scholar 

  4. Lee CH, Olson P, Evans RM. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 2003, 144: 2201–7.

    Article  PubMed  CAS  Google Scholar 

  5. Barroso I, Gurnell M, Crowley VE, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999, 402: 880–3.

    PubMed  CAS  Google Scholar 

  6. 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 insulin tropic mechanism distinct from glibencamide. Diabetologia 1998, 38: 24–30.

    Article  Google Scholar 

  7. Hunger R.H. Lipotoxicity in the pathogenesis of obesity- dependent NIDDM. Genetic and clinical implications. Diabetes 1995, 44: 863–70.

    Google Scholar 

  8. Kim HI, Cha JY, Kim SY, Kim JW, Roh KJ, Seong JK. Peroxisomal proliferator-activated receptor-ψ up-regulates glucokinase gene expression in gB-cell. Diabetes 2002, 51: 676–85.

    Article  PubMed  CAS  Google Scholar 

  9. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998, 391: 79–82.

    Article  PubMed  CAS  Google Scholar 

  10. Marx N, Sukhova G, Murphy C, Libby P, Plutzky J. Macrophages in human atheroma contain PPARgamma: differentiation- dependent peroxisomal proliferator-activated receptor gamma (PPAR gamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 1998, 153: 17–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Pritts EA, Zhao D, Ricke E, Waite L, Taylor RN. PPARψ decreases endometrial stromal cell transcription and translation of RANTES in vitro. J Clin Endocrinol Metab 2002, 87: 1841–4.

    PubMed  CAS  Google Scholar 

  12. Meier CA, Chicheportiche R, Juge-Aubry CE, Dreyer MG, Dayer JM. Regulation of the interleukin-1 receptor antagonist in THP-1 cells by peroxisome proliferator-activated receptor gamma. Cytokine 2002, 21: 320–8.

    Article  Google Scholar 

  13. Ogawa J, Takahashi S, Fujiwara T, et al. Troglitazone can prevent development of type 1 diabetes induced by multiple low-dose streptozotocin in mice. Life Sci 1999, 65: 1287–96.

    Article  PubMed  CAS  Google Scholar 

  14. Beales PE, Pozzilli P. Thiazolidinediones for the prevention of diabetes in the non-obese mouse: implications for human type 1 diabetes. Diabetes Metab Res Rev 2002, 18: 114–7.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang X, Young HA. Inhibition of biological functions of natural killer cells by 15-deoxy-Δ12,14-prostaglandin J2 through PPAR-ψ -dependent and -independent mechanism. FASEB J 2002, 16: A 1082.

    Google Scholar 

  16. Chinetti G, Griglio S, Antonucci M, et al. Activation of proliferator- activated receptors a and ψ induces apoptosis of human monocyte-derived macrophages. J Biol Chem 1998, 273: 25573–80.

    Article  PubMed  CAS  Google Scholar 

  17. Harris SG, Phipps RP. Prostaglandin D (2), its metabolite 15-d-PGJ (2), and peroxisome proliferator activated receptor-gamma agonists induce apoptosis in transformed, but not normal, human T lineage cells. Immunology 2002, 105: 23–4.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Zhang X, Young HA. PPAR and immune system- what do we know? Int Immunopharmacol 2002, 2: 1029–44.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Rotondi M, Lazzeri E, Romagnani P, Serio M. Role for interferon- ψ inducible chemokines in endocrine autoimmunity: an expanding field. J Endocrinol Invest 2002, 25: 177–80.

    Article  Google Scholar 

  20. Baker MS, Chen X, Rotramel AR, et al. Genetic deletion of chemokine receptor CXCR3 or antibody blockade of its ligand IP-10 modulates post transplantation graft-site lymphocytic infiltrates and prolongs functional graft survival in pancreatic islet allograft recipients. Surgery 2003, 134: 126–33.

    Article  PubMed  Google Scholar 

  21. Chinetti G, Fruchart JC, Staels B. Peroxisome proliferatoractivated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000, 49: 497–505.

    Article  PubMed  CAS  Google Scholar 

  22. Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001, 134: 61–71.

    Article  PubMed  CAS  Google Scholar 

  23. Collins AR, Meehan WP, Kintscher U, et al. Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and non-diabetic low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 2001, 21: 365–71.

    Article  PubMed  CAS  Google Scholar 

  24. Hsueh WA, Law RE. PPARψ and atherosclerosis: effects on cell growth and movement. Arterioscler Thromb Vasc Biol 2001, 21: 1891–5.

    Article  PubMed  CAS  Google Scholar 

  25. Jiang C, Ting AT, Seed B. PPARψ agonists inhibit production of monocyte inflammatory cytokines. Nature 1998, 391: 82–6.

    Article  PubMed  CAS  Google Scholar 

  26. Goetze S, Xi XP, Kawano H, et al. PPAR gamma-ligands inhibit migration mediated by multiple chemo attractant in vascular smooth muscle cells. J Cardiovasc Pharmacol 1999, 33: 798–806.

    Article  PubMed  CAS  Google Scholar 

  27. Marx N, Schonbeck U, Lazar MA, Libby P, Plutzky J. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998, 83: 1097–103.

    Article  PubMed  CAS  Google Scholar 

  28. Hattori Y, Hattori S, Kasai K. Troglitazone up regulates nitric oxide synthesis in vascular smooth muscle cells. Hypertension 1999, 33: 943–8.

    Article  PubMed  CAS  Google Scholar 

  29. Sugawara A, Takeuchi K, Uruno A, et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by PPARψ in vascular smooth muscle cells. Endocrinology 2001, 42: 3125–34.

    Google Scholar 

  30. Xin X, Yang S, Kowalsky J, Gerritsen ME. PPARψ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999, 274: 9116–21.

    Article  PubMed  CAS  Google Scholar 

  31. Calnek DS, Mazzella L, Roser S, Roman J, Hart CM. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 2003, 13: 52–7.

    Article  Google Scholar 

  32. Avena R, Mitchell ME, Nylen ES, Curry KM, Sidawy AN. Insulin action enhancement normalizes brachial artery vasoactivity in patients with peripheral vascular disease and occult diabetes. J Vasc Surg 1998, 28:1024–31.

    Article  PubMed  CAS  Google Scholar 

  33. Fukunaga Y, Itoh H, Doi K, et al. Thiazolidinediones, PPARψ agonists, regulate endothelial cell growth and secretion of vasoactive peptides. Atherosclerosis 2001, 158: 113–9.

    Article  PubMed  CAS  Google Scholar 

  34. Hattori Y, Hattori S, Kasai Kikuo. Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells. Hypertension 1999, 33: 943–8.

    Article  PubMed  CAS  Google Scholar 

  35. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease with type 2 diabetes mellitus. Circulation 2002, 106: 679–84.

    Article  PubMed  CAS  Google Scholar 

  36. Fonseca VA, Reynolds T, Hemphill D, Randolph C, Wall J, Valiquet TR. Effect of troglitazone on fibrinolysis and activated coagulation in patients with non-insulin-dependent diabetes mellitus. J Diabetes Complications 1998, 12: 181–6.

    Article  PubMed  CAS  Google Scholar 

  37. Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and apoE-deficient mice from atherosclerosis. J Biol Chem 2003, 278: 2461–8.

    Article  PubMed  CAS  Google Scholar 

  38. Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. European J Endocrinol 2003, 148: 293–300.

    Article  CAS  Google Scholar 

  39. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991, 88: 1785–92.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Cominacini L, Garbin U, Fratta Pasini A, et al. Troglitazone reduces LDL oxidation and lowers plasma E-selectin concentration in NIDDM patients. Diabetes 1998, 47: 130–3.

    Article  PubMed  CAS  Google Scholar 

  41. Iida KT, Kawakami Y, Shimano H, et al. Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rat. Am J Physiol Endocrinol Metab 2003, 284: E1125–E1130.

    PubMed  CAS  Google Scholar 

  42. Mehta JL, Hu B, Chen J, Li D. Pioglitazone inhibits LOX-1 expression in human coronary artery endothelial cells by reducing intracellular superoxide radical generation. Arterioscler Thromb Vasc Biol 2003, 23: 2203–8.

    Article  PubMed  CAS  Google Scholar 

  43. Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med 1998, 4: 1046–52.

    Article  PubMed  CAS  Google Scholar 

  44. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. PPAR gamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998, 93: 241–52.

    Article  PubMed  CAS  Google Scholar 

  45. Qiang X, Satoh J, Sagara M, et al. Inhibitory effect of troglitazone on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetologia 1998, 41: 1321–6.

    Article  PubMed  CAS  Google Scholar 

  46. Fujiwara T, Ohsawa T, Takahashi S, et al. Troglitazone, a new antidiabetic agent possessing radical scavenging ability, improved decreased skin blood flow in diabetic rats. Life Sci 1998, 63: 2039–47.

    Article  PubMed  CAS  Google Scholar 

  47. James SY, Lin F, Kolluri SK, Dawson MI, Zhang SK. Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells. Cancer Res 2003, 63: 3531–8.

    PubMed  CAS  Google Scholar 

  48. Altiok S, Xu M, Spiegelman BM. PPARψ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down regulation of PP2A. Genes Dev 1997, 11: 1987–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  49. Qin C, Burghardt R, Smith R, Wormke M, Stewart J, Jafe S. Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells. Cancer Res 2003, 63: 958–64.

    PubMed  CAS  Google Scholar 

  50. Bishop-Bailey D, Hla T. Endothelial cell apoptosis induced by the PPAR ligand 15-eoxy-prostaglandin J2. J Biol Chem 1999, 274: 17042–8.

    Article  PubMed  CAS  Google Scholar 

  51. Inoue K, Kawahito Y, Tsubouchi Y, et al. Expression of peroxisome proliferator-activated receptor (PPAR)-gamma in human lung cancer. Anticancer Res 2001, 21: 2471–6.

    PubMed  CAS  Google Scholar 

  52. Panigraphy D, Singer S, Shen LQ, et al. PPARψ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 2002, 110: 923–32.

    Article  Google Scholar 

  53. Palakurthi SS, Antas H, Grubissich LM, Mortensen RM, Halperin JA. Anticancer effects of thiazolidinediones are independent of PPARψ and mediated by inhibition of translation initiation. Cancer Res 2001, 15: 6213–8.

    Google Scholar 

  54. Saez E, Tontonoz P, Nelson MC, et al. Activators of the nuclear receptor PPARψ enhance colon polyp formation. Nat Med 1998, 4: 1058–61.

    Article  PubMed  CAS  Google Scholar 

  55. Holden PR, Tugwood JD. Peroxisome proliferator-activated receptor a: role in rodent liver cancer and species differences. Mol Endocrinol 1999, 22: 1–8.

    Article  CAS  Google Scholar 

  56. Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPARψ1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 2002, 87: 3947–52.

    PubMed  CAS  Google Scholar 

  57. Martelli ML, Iuliano R, Le Pera I, et al. Inhibitory effects of peroxisome proliferator-activated receptors ψ on thyroid carcinoma cell growth. J Clin Endocrinol Metab 87: 4728–35.

  58. Heaney AP, Fernando M, Yong WH, Melmed S. Functional PPAR-ψ receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nature Med 2002, 8: 1281–7.

    Article  PubMed  CAS  Google Scholar 

  59. Heaney AP, Fernando M, Melmed S. PPAR-ψ receptor ligands: novel therapy for pituitary adenomas. J Clin Invest 2003, 111: 1381–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Heaney AP, Fernando M, Melmed S. PPAR-ψ receptor ligands: novel therapy for pituitary adenomas. J Clin Invest 2003, 111: 1381–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  61. Yoshioka S, Nishino H, Shiraki T, et al. Antipertensive effects of CS-045 treatment in obese Zucker rats. Metabolism 1993, 42: 75–80.

    Article  PubMed  CAS  Google Scholar 

  62. Ogihara T, Rakugi H, Ikegami H, Mikami H, Masuo K. Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. Am J Hypertens 1995, 8: 316–20.

    Article  PubMed  CAS  Google Scholar 

  63. Song J, Walsh MF, Igwe R, Ram IL, Barazi M, Dominguez LJ. Troglitazone reduces contraction by inhibition of vascular smooth muscle cell Ca 2+ currents and not endothelial nitric oxide production. Diabetes 1997, 46: 659–64.

    Article  PubMed  CAS  Google Scholar 

  64. Kawasaki J, Hirano K, Nishimura J, Fujishima M, Kanaide H. Mechanism of vasorelaxation induced by troglitazone, a novel antidiabetic drug in the porcine coronary artery. Circulation 1998, 98: 2446–52.

    Article  PubMed  CAS  Google Scholar 

  65. Murakami T, Mizuno S, Ohsato K, et al. Effects of troglitazone on frequency of coronary vasospastic-induced angina pectoris in patients with diabetes mellitus. Am J Cardiol 1999, 84: 92–4.

    Article  PubMed  CAS  Google Scholar 

  66. Shimoyama M, Ogino K, Tanaka Y, Ikeda T, Hisatome I. Hemodynamic basis for the acute cardiac effects of troglitazone in isolated perfused rat hearts. Diabetes 1999, 48: 609–15.

    Article  PubMed  CAS  Google Scholar 

  67. Krentz AJ, Bailey CJ, Melander A.. Thiazolidinediones for type 2 diabetes. New agents reduce insulin resistance but need long-term clinical trials. B. M. J. 2000, 321: 252–3.

    Article  CAS  Google Scholar 

  68. Everet L, Galli A, Crabb D. The role of hepatic peroxisome proliferator activated receptors (PPARs) in health and disease. Liver 2000, 20: 191–9.

    Article  Google Scholar 

  69. Boelteri UA, Bedoucha M. Toxicological consequences of peroxisome proliferator receptor ψ (PPARψ) expression in the liver: insights from models of obesity and type 2 diabetes. Biochem Pharmacol 2002, 63: 1–10.

    Article  Google Scholar 

  70. Uchimura K, Nakamuta M, Enjoji M, et al. Activation of retinoic X receptor and peroxisome proliferator-activated receptor ψ inhibits nitric oxide and tumor necrosis factor alpha production in rat Kupffer cells. Hepatology 2001, 33: 91–9.

    Article  PubMed  CAS  Google Scholar 

  71. Marra F, Efsen E, Romanelli RG, et al. Ligands of peroxisome proliferator activated receptor ψ modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Hepatology 2000, 119: 466–79.

    CAS  Google Scholar 

  72. Galli A, Crabb D, Price D, et al. Peroxisome proliferator activated receptor ψ transcriptional regulation is involved in PDGF-induced proliferation in human hepatic stellate cells. Hepatology 2000, 31: 101–8.

    Article  PubMed  CAS  Google Scholar 

  73. Galli A, Crabb DW, Ceni E, et al. Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cells activation in vivo and in vitro. Gastroenterology 2002, 122: 1924–40.

    Article  PubMed  CAS  Google Scholar 

  74. Bedoucha M, Atpodien E, Boelsterli UA. Diabetic KKAy mice increased hepatic PPARψ1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones. J Hepatol 2001, 35: 17–23.

    Article  PubMed  CAS  Google Scholar 

  75. Jia DM, Akiyama T, Fukumitsu KI, Tabaru A, Otsuki M. Troglitazone prevents fatty changes of the liver of obese diabetic rat. Gastroenterology 2001, 120 (5 suppl 1): A220.

    Google Scholar 

  76. Cadwell SH, Hespenheide EE, Redick JA, Iezzoni JC, Battle EH, Sheppard BL. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol 2001, 96: 519–25.

    Article  Google Scholar 

  77. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Sponseller CA, Hampton K, Bacon BR. Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis. J Hepatol 2003, 38: 434–40.

    Article  PubMed  CAS  Google Scholar 

  78. Ceni E, Crabb DW, Mello T, et al. Antidiabetic thiazolidinediones inhibit hepatic tumor formation in HBV trangenic mouse model. Hepathology 2003, 38: 400A (abstract).

    Google Scholar 

  79. Fischer B, von Knethen A, Brune B. Dualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: role of Peroxisome Proliferator-Activated Receptor-ψ. The Journal of Immunology 2002, 168:2828–34.

    Article  PubMed  CAS  Google Scholar 

  80. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998, 47: 859–66.

    Article  PubMed  CAS  Google Scholar 

  81. Nicholas SB, Kawano Y, Wakino S, Collins AR, Hsueh WA. Expression and function of peroxisome proliferator-activated receptor-ψ in mesangial cells. Hypertension 2001, 37: 722–7.

    Article  PubMed  CAS  Google Scholar 

  82. Zheng F, Fornoni A, Elliot SJ, et al. Upregulation of type I collagen by TGFgB in mesangial cells is blocked by PPARψ activation. Am J Physiol 2002, 282: F639–648.

    Article  CAS  Google Scholar 

  83. Weigert C, Brodbeck, Bierhaus A, Haring HU, Schleicher ED. C-Fos-driven transcriptional activation of TGF beta-1: inhibition of high glucose-induced promoter activity by thiazolidinediones. Biochem Biophys Res Commun 2003, 304: 301–7.

    Article  PubMed  CAS  Google Scholar 

  84. Fujii M, Takemura R, Yamaguchi M, Hasegawa G, Shigeta H, Nakano K, et al. Troglitazone (CS-045) ameliorates albuminuria in streptozotocin-induced diabetic rats. Metabolism 1997, 46: 981–3.

    Article  PubMed  CAS  Google Scholar 

  85. Imano E, Kanda T, Nakatami Y, et al. Effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy. Diabetes Care. 1998, 21: 2135–9.

    Article  PubMed  CAS  Google Scholar 

  86. Yamashita H, Nagai Y, Takamura T, Nohaya E, Kobayashi K. Thiazolidinediones derivates ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rats. Metabolism 2002, 51: 403–8.

    Article  PubMed  CAS  Google Scholar 

  87. Bakris G, Viberti G, Weston WM, Heise H, Porter LE, Freed MI. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J of Hum Hypertension 2003, 17: 7–12.

    Article  CAS  Google Scholar 

  88. Nakamura T, Ushiyama C, Osada S, Hara M, Shimada N, Koide H. Pioglitazone reduces urinary podocytes excretion in type 2 diabetes patients with microalbuminuria. Metabolism 2001, 50: 1193–6.

    Article  PubMed  CAS  Google Scholar 

  89. Emoto M, Anno T, Sato Y, et al. Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes. Diabetes 2001, 50:1166–70.

    Article  PubMed  CAS  Google Scholar 

  90. Murata T, Hata Y, Kim S, Hsueh WA, Law RE, Hinton DR. Response of experimental retinal neovascularization to thiazolidinediones. Arch Ophthalmol 2001, 119: 709–17.

    Article  PubMed  CAS  Google Scholar 

  91. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponenctin receptors that mediate antidiabetic metabolic effects. Nature 2003, 423: 762–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Giannini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giannini, S., Serio, M. & Galli, A. Pleiotropic effects of thiazolidinediones: Taking a look beyond antidiabetic activity. J Endocrinol Invest 27, 982–991 (2004). https://doi.org/10.1007/BF03347546

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347546

Key-words

Navigation