Role of PPARγ in renoprotection in type 2 diabetes: Molecular mechanisms and therapeutic potential

Clinical Science

Volumn 116, Issue 1, 2009, Pages 17-26

  Yang, Jichun ^a   Zhang, Dongjuan ^a   Li, Jing ^a   Zhang, Xiaoyan ^a   Fan, Fenling ^a   Guan, Youfei ^a  

^a PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

Author keywords

Chronic kidney disease; Diabetic nephropathy; Peroxisome proliferator activated receptor (PPAR); Renoprotection; Type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADIPONECTIN; INSULIN; INTERCELLULAR ADHESION MOLECULE 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; ROSIGLITAZONE; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR ALPHA; ANTIINFLAMMATORY AGENT;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BLOOD PRESSURE REGULATION; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; DIABETIC NEPHROPATHY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC RISK; GLYCEMIC CONTROL; HUMAN; INSULIN RESISTANCE; LIPID STORAGE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RENAL PROTECTION; REVIEW; ANIMAL; DISEASE MODEL; DRUG EFFECT; KIDNEY; LIPID METABOLISM; METABOLISM; MOUSE; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT;

ADIPONECTIN; ANIMALS; ANTI-INFLAMMATORY AGENTS; DIABETES MELLITUS, TYPE 2; DIABETIC NEPHROPATHIES; DISEASE MODELS, ANIMAL; HUMANS; INSULIN RESISTANCE; KIDNEY; LIPID METABOLISM; MICE; PPAR GAMMA; RATS; THIAZOLIDINEDIONES;

EID: 60549085974     PISSN: 01435221     EISSN: None     Source Type: Journal    
DOI: 10.1042/CS20070462     Document Type: Review

References (131)

1. Wild, S., Roglic, G., Green, A., Sicree, R. and King, H. (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047-1053
2. Zheng, F. and Guan, Y. (2007) Thiazolidinediones: a novel class of drugs for the prevention of diabetic nephropathy? Kidney Int. 72, 1301-1303
3. Sarafidis, P. A. and Bakris, G. L. (2006) Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int. 70, 1223-1233
4. Lehrke, M. and Lazar, M. A. (2005) The many faces of PPARγ. Cell 123, 993-999
5. Balakumar, P., Rose, M. and Singh, M. (2007) PPAR ligands: are they potential agents for cardiovascular disorders? Pharmacology 80, 1-10
6. Guan, Y. (2004) Peroxisome proliferator-activated receptor family and its relationship to renal complications of the metabolic syndrome. J. Am. Soc. Nephrol. 15, 2801-2815
7. Tonelli, J., Li, W., Kishore, P. et al. (2004) Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 53, 1621-1629
8. Kanatani, Y., Usui, I., Ishizuka, K. et al. (2007) Effects of pioglitazone on suppressor of cytokine signaling 3 expression: potential mechanisms for its effects on insulin sensitivity and adiponectin expression. Diabetes 56, 795-803
9. Miyazaki, Y., Cersosimo, E., Triplitt, C. and DeFronzo, R. A. (2007) Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int. 72, 1367-1373
10. Okada, T., Wada, J., Hida, K. et al. (2006) Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms. Diabetes 55, 1666-1677
11. Yozai, K., Shikata, K., Sasaki, M. et al. (2005) Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions. J. Am. Soc. Nephrol. 16, 3326-3338
12. Tuttle, K. R. (2005) Linking metabolism and immunology: diabetic nephropathy is an inflammatory disease. J. Am. Soc. Nephrol. 16, 1537-1538
13. Vionnet, N., Tregouet, D., Kazeem, G. et al. (2006) Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene. Diabetes 55, 3166-3174
14. Wang, Z.Jiang, T., Li, J. et al. (2005) Regulation of renal lipid metabolism, lipid accumulation, and gomerulosclerosis in FVB db/db mice with type 2 diabetes. Diabetes 54, 2328-2335
15. Zhang, Y. and Guan, Y. (2005) PPAR-γ agonist and diabetic nephropathy. Curr. Diabetes Rep. 5, 470-475
16. Kollerits, B., Fliser, D., Heid, I. M., Ritz, E. and Kronenberg, F. (2007) Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study. Kidney Int. 71, 1279-1286
17. Ruan, X. Z, rMoorhead, J. F., Fernando, R., Wheelers D. C., Powis, S. H. and Varghese, Z. (2003) PPAR agonists protect mesangial cells from interleukin 1β-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway. J. Am. Soc. Nephrol. 14, 593-600
18. Schrier, R. W., Estacio, R. O., Mehler, P. S. and Hiatt, W. R. (2007) Appropriate blood pressure control in - hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial. Nat. Clin. Pract. Nephrol. 3, 428-438
19. Chawla, A., Schwarz, E. J., Dimaculangan, D. D. and Lazar, M. A. (1994) Peroxisome proliferator-activated receptor (PPAR) γ: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135, 798-800
20. Guan, Y., Zhang, Y., Schneider, A., Davis, L., Breyer, R. M. and Breyer, M. D. (2001) Peroxisome proliferator-activated receptor-γ activity is associated with renal microvasculature. Am. J. Physiol. Renal. Physiol. 281, R1036-R1046
21. Law, R. E., Goetze, S., Xi, X. P. et al. (2000) Expression and function of PPARγ in rat and human vascular smooth muscle cells. Circulation 101, 1311-1318
22. Guan, Y., Zhang, Y., Davis, L. and Breyer, M. D. (1997) Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans. Am. J. Physiol. 273, F1013-F1022
23. Yang, T., Michele, D. E., Park, J. et al. (1999) Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney. Am. J. Physiol. 277, F966-F973
24. Nicholas, S. B., Kawano, Y., Wakino, S., Collins, A. R. and Hsueh, W. A. (2001) Expression and function of peroxisome proliferator-activated receptor-γ in mesangial cells. Hypertension 37, 722-727
25. Asano, T., Wakisaka, M., Yoshinari, M. et al. (2000) Peroxisome proliferator-activated receptor γ 1 (PPARγ 1) expresses in rat mesangial cells and PPARγ agonists modulate its differentiation. Biochim. Biophys. Acta 1497, 148-154
26. Zafiriou, S., Stanners, S. R., Saad, S., Polhill, T. S., Poronnik, P. and Pollock, C. A. (2005) Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J. Am. Soc. Nephrol. 16, 638-645
27. Li, H., Ruan, X. Z., Powis, S. H. et al. (2005) EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells evidence for a PPAR-γ-dependent mechanism. Kidney Int. 67, 867-874
28. Baylis, C., Atzpodien, E. A., Freshour, G. and Engels, K. (2003) Peroxisome proliferator-activated receptor γ agonist provides superior renal protection versus angiotensin-converting enzyme inhibition in a rat model of type 2 diabetes with obesity. J. Pharmacol. Exp. Ther. 307, 854-860
29. Fujita, A., Sasaki, H., Doi, A. et al. (2008) Ferulic acid prevents pathological and functional abnormalities of the kidney in Otsuka Long-Evans Tokushima Fatty diabetic rats. Diabetes Res. Clin. Pract. 79, 11-17
30. Weigert, C., Brodbeck, K., Bierhaus, A., Haring, H. U. and Scleicher, E. D. (2003) c-Fos-driven transcriptional activation of transforming growth factor β-1: inhibition of high glucose-induced promoter activity by thiazolidinediones. Biochem. Biophys. Res. Commun. 304, 301-307
31. Zheng, F., Fornoni, A., Elliot, S. J. et al. (2002) Upregulation of type I collagen by TGF-β in mesangial cells is blocked by. PPAR γ activation. Am. J. Physiol. Renal Physiol. 282, F639-F648
32. Weissgarten, J., Berman, S., Efrati, S., Rapoport, M., Averbukh, Z. and Feldman, L. (2006) Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of rosiglitazone-treated pregnant diabetic rats. Nephrol. Dial. Transplant. 21, 1198-1204
33. Ohga, S., Shikata, K., Yozai, K. et al.{2007) Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-κB activation. Am. J. Physiol. Renal Physiol. 292, F1141-F1150
34. Zafiriou, S., Stanners, S. R., Saad, S., Polhill, T. S., Poromiik, P. and Pollock, C. A. (2005) Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J. Am. Soc. Nephrol. 16, 638-645
35. Nakamura, T., Ushiyama, C., Suzuki, S. et al. (2001) Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentrations in Type 2 diabetic patients with microalbuminuria or macroalbuminuria. Diabetic Med. 18, 308-313
36. Agarwal, R., Saha, C., Battiwala, M. et al. (2005) A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy. Kidney Int. 68, 285-292
37. Sarafidis, P. A., Lasaridis, A. N., Nilsson, P. M. et al. (2005) The effect of rosiglitazone on urine albumin excretion in patients with type 2 diabetes mellitus and hypertension. Am. J. Hypertens. 18, 227-234
38. Pistrosch, F., Herbrig, K., Kindel, B., Passauer, J., Fischer, S. and Gross, P. (2005) Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes 54, 2206-2211
39. Imano, E., Kanda, T., Nakatani, Y., Nishida, T. et al. (1998) Effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy. Diabetes Care 21, 2135-2139
40. Nakamura, T., Ushiyama, C., Shimada, N., Hayashi, K., Ebihara, I. and Koide, H. (2000) Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients. J. Diabetes Complications 14, 250-254
41. Yao, Q., Nordfors, L., Axelsson, J. et al. (2005) Peroxisome proliferator-activated receptor γ polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy. Atherosclerosis 182, 105-111
42. Pollex, R. L., Mamakeesick, M., Zinman, B., Harris, S. B., Hegele, R. A. and Hanley, A. J. (2007) Peroxisome proliferator-activated receptor γ polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes. J. Diabetes Complications 21, 166-171
43. Gurnell, M. (2005) Peroxisome proliferator-activated receptor and the regulation of adipocyte function: lessons from human genetic studies. Best Pract. Res. Clin. Endocrinol. Metab. 19, 501-523
44. Barroso, I., Gurnell, M., Crowley, V. E. et al. (1999) Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880-883
45. Semple, R. K., Chatterjee, V. K. and O'Rahilly, S. (2006) PPAR γ and human metabolic disease. J. Clin. Invest. 116, 581-589
46. UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837-853
47. Writing Team for the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy; the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA, J. Am. Med Assoc. 290, 2159-2167
48. Larkins, R. G. and Dunlop, M. E. (1992) The link between hyperglycaemia and diabetic nephropathy. Diabetologia 35, 499-504
49. Fioretto, P., Bruseghin, M., Berto, I., Gallina, P., Manzato, E. and Mussap, M. (2006) Renal protection in diabetes: role of glycemic control. J. Am. Soc. Nephrol. 17, 86-89
50. Allard, J., Buleon, M., Cellier, E. et al. (2007) ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats. Am. J. Physiol. Renal Physiol. 293, F1083-F1092
51. Sechi, L. A., De Carli, S. and Bartoli, E. (1994) In situ characterization of renal insulin receptors in the rat. J. Recept. Res. 14, 347-356
52. Jiang, G., Dallas-Yang, Q., Liu, F., Moller, D. E. and Zhang, B. B. (2003) Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)- and tumor necrosis factor α (TNFα)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells. J. Biol. Chem. 278, 180-186
53. Tiwari, S., Halagappa, V. K., Riazi, S., Hu, X. and Ecelbarger, C. A. (2007) Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. J. Am. Soc. Nephrol. 18, 2661-2671
54. Coward, R. J., Welsh, G. I., Yang, J. et al. (2005) The human glomerular podocyte is a novel target for insulin action. Diabetes 54, 3095-3102
55. Tiwari, S., Nordquist, L., Halagappa, V. K. and Ecelbarger, C. A. (2007) Trafficking of ENaC subunits in response to acute insulin in mouse kidney. Am. J. Physiol. Renal Physiol. 293, F178-F185
56. Tiwari, S., Riazi, S. and Ecelbarger, C. A. (2007) Insulin's impact on renal sodium transport and blood pressure in health, obesity, and diabetes. Am. J. Physiol. Renal Physiol. 293, F974-F984
57. Ohtomo, S., Izuhara, Y., Takizawa, S. et al. (2007) Thiazolidinediones provide better renoprotection than insulin in an obese, hypertensive type II diabetic rat model. Kidney Int. 72, 1512-1519
58. Tiwari, S., Halagappa, V. K., Riezi, S., Hu, X. and Ecelbarger, C. A. (2007) Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. J. Am. Soc. Nephrol. 18, 2661-2671
59. Yuan, M., Konstantopoulos, N., Lee, J. et al. (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293, 1673-1677
60. Reference deleted
61. Shankland, S. J. and Wolf, G. (2000) Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. Am. J. Physiol. Renal Physiol. 278, F515-F529
62. Preisig, P. A. and Franch, H. A. (1995) Renal epithelial cell hyperplasia and hypertrophy. Semin. Nephrol. 15, 327-340
63. Griffin, S. V., Pichler, R., Dittrich, M., Durvasula, R. and Shankland, S. J. (2003) Cell cycle control in glomerular disease. Springer Semin. Immunopathol. 24, 441-457
64. Griffin, S. V., Pichler, R., Wada, T., Vaughan, M., Durvasula, R. and Shankland, S. J. (2003) The role of cell cycle proteins in glomerular disease. Semin. Nephrol. 23, 569-582
65. Monkawa, T, Hiromura, K., Wolf, G. and Shankland, S. J. (2002) The hypertrophic effect of transforming growth factor-β is reduced in the absence of cyclin-dependent kinase-inhibitors p21 and p27. J. Am. Soc. Nephrol. 13, 1172-1178
66. Kip1 ameliorates progression of diabetic nephropathy. J. Am. Soc. Nephrol. 14, 699-708
67. Huang, J. S., Chuang, L. Y., Guh, J. Y., Huang, Y. J. and Hsu, M. S. (2007) Antioxidants attenuate high glucose-induced hypertrophic growth in renal tubular epithelial cells. Am. J. Physiol. Renal Physiol. 293, F1072-F1082
68. WAF1, CIP1 is increased in experimental diabetic nephropathy: potential role in glomerular hypertrophy. J. Am. Soc. Nephrol. 9, 986-993
69. Kip1 in diabetic db/db mouse: role of hyperglycemia. Kidney Int. 53, 869-879
70. Masson, E., Lagarde, M., Wiernsperger, N. and El Bawab, S. (2006) Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and hypertrophy: common or independent mechanisms? IUBMB Life 58, 381-388
71. Hu, E., Liang, P. and Spiegelman, B. M. (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271, 10697-10703
72. Nedvidkova, J., Smitka, K., Kopsky, V. and Hainer, V. (2005) Adiponectin, an adipocyte-derived protein. Physiol. Res. 54, 133-140
73. Menzaghi, C., Trischitta, V. and Doria, A. (2007) Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 56, 1198-1209
74. Kubota, N., Terauchi, Y., Kubota, T. et al. (2006) Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J. Biol. Chem. 281, 8748-8755
75. Lindsay, R. S., Funahashi, T., Hanson, R. L. et al. (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360, 57-58
76. Fujita, H., Morii, T., Koshimura, J. et al. (2006) Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy. Endocr. J. 53, 745-752
77. Guo, Z. and Zhao, Z. (2007) Effect of N-acetylcysteine on plasma adiponectin and renal adiponectin receptors in streptozotocin-induced diabetic rats. Eur. J. Pharmacol. 558, 208-213
78. Sun, X., Han, R., Wang, Z. and Chen, Y. (2006) Regulation of adiponectin receptors in hepatocytes by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone. Diabetologia 49, 1303-1310
79. Tsuchida, A., Yamauchi, T., Takekawa, S. et al. (2005) Peroxisome proliferator-activated receptor (PPAR)α activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARα, PPARγ, and their combination. Diabetes 54, 3358-3370
80. Cha, D. R., Zhang, X., Zhang, Y. et al. (2007) Peroxisome proliferator activated receptor α/γ dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice. Diabetes 56, 2036-2045
81. Seliger, S. L. (2006) Inflammation and dyslipidemia in nephropathy: an epidemiologic perspective. Kidney Int. 69, 206-208
82. Hirata, K., Shikata, K., Matsuda, M. et al. (1998) Increased expression of selectins in kidneys of patients with diabetic nephropathy. Diabetologia 41, 185-192
83. Okada, S., Shikata, K., Matsuda, M. et al. (2003) Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes. Diabetes 52, 2586-2593
84. Shikata, K. and Makino, H. (2001) Role of macrophages in the pathogenesis of diabetic nephropathy. Contrib. Nephrol. 46-54
85. Sugimoto, H., Shikata, K., Hirata, K. et al. (1997) Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes 46, 2075-2081
86. Lee, S., Kim, W., Moon, S. O. et al. (2006) Rosiglitazone ameliorates cisplatin-induced renal injury in mice. Nephrol. Dial. Transplant. 21, 2096-2105
87. Tang, S. C., Leung, J. C., Chan, L. Y., Tsang, A. W. and Lai, K. N. (2006) Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-γ agonist. J. Am. Soc. Nephrol. 17, 1633-1643
88. Jiang, C., Ting, A. T. and Seed, B. (1998) PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82-86.
89. Shah, S. V., Baliga, R., Rajapurkar, M. and Fonseca, V. A. (2007) Oxidants in chronic kidney disease. J. Am. Soc. Nephrol. 18, 16-28
90. Araujo, M. and Welch, W. J. (2006) Oxidative stress and nitric oxide in kidney function. Curr. Opin. Nephrol. Hypertens. 15, 72-77
91. Prabhakar, S., Starnes, J., Shi, S., Lonis, B. and Tran, R. (2007) Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J. Am. Soc. Nephrol. 18, 2945-2952
92. Sommer, M. and Wolf, G. (2007) Rosiglitazone increases PPARγ in renal tubular epithelial cells and protects against damage by hydrogen peroxide. Am. J. Nephrol. 27, 425-434
93. Sung, B., Park, S., Yu, B. P. and Chung, H. Y. (2006) Amelioration of age-related inflammation and oxidative stress by PPARγ activator: suppression of NF-κB by 2,4-thiazolidinedione. Exp. Gerontol. 41, 590-599
94. Sivarajah, A., Chatterjee, P. K., Patel, N. S. et al. (2003) Agonists of peroxisome-proliferator activated receptor-γ reduce renal ischemia/ reperfusion injury. Am. J. Nephrol. 23, 267-276
95. Jandeleit-Dahm, K., Cao, Z., Cox, A. J., Kelly, D. J., Gilbert, R. E. and Cooper, M. E. (1999) Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int. Suppl. 71, 31-36
96. Abrass, C. K. (2004) Cellular lipid metabolism and the role of lipids in progressive renal disease. Am. J. Nephrol. 24, 46-53
97. Ishigaki, N., Yamamoto, T., Shimizu, Y. et al. (2007) Involvement of glomerular SREBP-1c in diabetic nephropathy. Biochem. Biophys. Res. Commun. 364, 502-508
98. Proctor, G., Jiang, T., Iwahashi, M., Wang, Z., Li, J. and Levi, M. (2006) Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetes. Diabetes 55, 2502-2509
99. Lehrke, M., Pascual, G., Glass, C. K. and Lazar, M. A. (2005) Gaining weight: the Keystone Symposium on PPAR and LXR. Genes Dev. 19, 1737-1742
100. Wu, J., Zhang, Y., Wang, N. et al. (2004) Liver X receptor-α mediates cholesterol efflux in glomerular mesangial cells. Am. J. Physiol. Renal Physiol. 287, F886-F895
101. Zhang, Y., Zhang, X., Chen, L. et al. (2006) Liver X receptor agonist TO-901317 upregulates SCD1 expression in renal proximal straight tubule. Am. J. Physiol. Renal Physiol. 290, F1065-F1073
102. Fiorucci, S., Rizzo, G., Antonelli, E. et al. (2005) Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor γ contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. J. Pharmacol. Exp. Ther. 315, 58-68
103. Palmer, A. J., Roze, S., Rodby, R. A., Valentine, W. J., Ritz, E. and Lehnert, H. (2006) Clinical and health economic implications of early treatment with irbesartan of patients with type 2 diabetes mellitus, hypertension and nephropathy. Deutsch. Med. Wochenschr. 131, 1721-1726
104. UK Prospective Diabetes Study Group (1998) Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br. Med. J. 317, 703-713
105. Andersen, S., Brochner-Mortensen, J. and Parving, H. H. (2003) Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria. Diabetes Care 26, 3296-3302
106. Duan, S. Z., Ivashchenko, C. Y., Whitesall, S. E. et al. (2007) Hypotension, lipodystrophy, and insulin resistance in generalized PPARγ-deficient mice rescued from embryonic lethality. J. Clin. Invest. 117, 812-822
107. Todorov, V. T., Desch, M., Schmitt-Nilson, N., Todorova, A. and Kurtz, A. (2007) Peroxisome proliferator-activated receptor-γ is involved in the control of renin gene expression. Hypertension 50, 939-944
108. Inzucchi, S. E., Maggs, D. G., Spollett, G. R. et al. (1998) Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N. Engl. J. Med. 338, 867-872
109. Saku, K., Zhang, B., Ohta, T. and Arakawa, K. (1997) Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits. Am. J. Hypertens. 10, 1027-1033
110. Yoshimoto, T., Naruse, M., Nishikawa, M. et al. (1997) Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. Am. J. Physiol. 272, E989-E996
111. Walker, A. B., Chattington, P. D., Buckingham, R. E. and Williams, G. (1999) The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Diabetes 48, 1448-1453
112. Goya, K., Sumitani, S., Otsuki, M. et al. (2006) The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells. J. Diabetes Complications 20, 336-342
113. Efrati, S., Berman, S., Ilgiyeav, E., Averbukh, Z. and Weissgarten, J. (2007) PPAR-γ activation inhibits angiotensin II synthesis, apoptosis, and proliferation of mesangial cells from spontaneously hypertensive rats. Nephron Exp. Nephrol. 106, 107-112
114. Yousefipour, Z., Hercule, H., Truong, L., Oyekan, A. and Newaz, M. (2007) Ciglitazone, a peroxisome proliferator-activated receptor γ inducer, ameliorates renal preglomerular production and activity of angiotensin II and thromboxane A2 in glycerol-induced acute renal failure. J. Pharmacol. Exp. Ther. 322, 461-468
115. Takeda, K., Ichiki, X., Tokunou, T. et al. (2000) Peroxisome proliferator-activated receptor γ activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation 102, 1834-1839
116. Gong, W., Liu, Z. H., Zeng, C. H. et al. (2007) Amylin deposition in the kidney of patients with diabetic nephropathy. Kidney Int 72, 213-218
117. Wookey, P. J., Cao, Z. and Cooper, M. E. (1998) Interaction of the renal amylin and renin-angiotensin systems in animal models of diabetes and hypertension. Miner. Electrolyte Metab. 24, 389-399
118. Kahn,S. E., D'Alessio, D. A., Schwartz, M. W. et al. (1990) Evidence of cosecretion of islet amyloid polypeptide and insulin by β-cells. Diabetes 39, 634-638
119. Ogawa, A., Harris, V, McCorkle, S. K., Unger, R. H. and Luskey, K. L. (1990) Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment. J. Clin. Invest. 85, 973-976
120. Yang, J., Robert, C. E., Burkhardt, B. R. et al. (2005) Mechanisms of glucose-induced secretion of pancreatic-derived factor (PANDER or FAM3B) in pancreatic β-cells. Diabetes 54, 3217-3228
121. Kautzky-Willer, A., Thomaseth, K., Ludvik, B. et al. (1997) Elevated islet amyloid pancreatic polypeptide and proinsulin in lean gestational diabetes. Diabetes 46, 607-614
122. Mulder, H., Ahren, B. and Sundler, F. (1996) Islet amyloid polypeptide and insulin gene expression are regulated in parallel by glucose in vivo in rats. Am. J. Physiol. 271, E1008-E1014
123. Peng, A., Liu, Z. H., Zhou, H., Zhu, M. Y. and Li, L. S. (2007) Fibrillogenic amylin evokes the apoptosis of human mesangial cells. Diabetes Res. Clin. Pract. 78, 16-22
124. Ikeda, T., Iwata, K. and Ochi, H. (2001) Effect of insulin, proinsulin, and amylin on renin release from perfused rat kidney. Metab. Clin. Exp. 50, 763-766
125. Zapecka-Dubno, B., Czyzyk, A., Dworak, A. and Bak, M. I. (1999) Effect of oral antidiabetic agents on plasma amylin level in patients with non-insulin-dependent diabetes mellitus (type 2). Arzneimittelforschung 49, 330-334
126. Lin, C. Y., Gurlo, T., Haataja, L., Hsueh, W. A. and Butler, P. C. (2005) Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone protects human islet cells against human islet amyloid polypeptide toxicity by a phosphatidylinositol 3′-kinase-dependent pathway. J. Clin. Endocrinol. Metab. 90, 6678-6686
127. Hull, R. L., Shen, Z. P., Watts, M. R. et al. (2005) Long-term treatment with rosiglitazone and metformin reduces the extent of, but does not prevent, islet amyloid deposition in mice expressing the gene for human islet amyloid polypeptide. Diabetes 54, 2235-2244
128. Ruan, X., Zheng, F. and Guan, Y. (2008) PPARs and the kidney in metabolic syndrome. Am. J. Physiol. Renal Physiol. 294, F1032-F1047
129. Guan, Y., Hao, C., Cha, D. R. et al. (2005) Thiazolidinediones expand body fluid volume through PPARγ stimulation of ENaC-mediated renal salt absorption. Nat. Med. 11, 861-866
130. Zhang, H., Zhang, A., Kohan, D. E., Nelson, R. D., Gonzalez, F. J. and Yang, T. (2005) Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention. Proc. Natl. Acad. Sci. U.S.A. 102, 9406-9411
131. Nissen, S. E. and Wolski, K. (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med. 356, 2457-2471