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Cell Growth and Development

Targeted Elimination of Peroxisome Proliferator-Activated Receptor γ in β Cells Leads to Abnormalities in Islet Mass without Compromising Glucose Homeostasis

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Pages 7222-7229 | Received 15 Jan 2003, Accepted 07 Jul 2003, Published online: 27 Mar 2023

REFERENCES

  • Accili, D. 2001. A kinase in the life of the beta cell. J. Clin. Investig. 108: 1575–1576.
  • Akiyama, T. E., S. Sakai, G. Lambert, C. J. Nicol, K. Matsusue, S. Pimprale, Y.-H. Lee, M. Ricote, C. K. Glass, H. B. Brewer, Jr., and F. J. Gonzalez. 2002. Conditional disruption of the peroxisome proliferator-activated receptor γ gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol. Cell. Biol. 22: 2607–2619.
  • Araki, E., M. A. Lipes, M. E. Patti, J. C. Bruning, B. Haag III, R. S. Johnson, and C. R. Kahn. 1994. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372: 186–190.
  • Aspinwall, C. A., W.-J. Qian, M. G. Roper, R. N. Kulkarni, C. R. Kahn, and R. T. Kennedy. 2000. Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in β-cells. J. Biol. Chem. 275: 22331–22338.
  • Barak, Y., M. C. Nelson, E. S. Ong, Y. Z. Jones, P. Ruiz-Lozano, K. R. Chien, A. Koder, and R. M. Evans. 1999. PPARγ is required for placental, cardiac, and adipose tissue development. Mol. Cell 4: 585–595.
  • Berkowitz, K., R. Peters, S. L. Kjos, J. Goico, A. Marroquin, M. E. Dunn, A. Xiang, S. Azen, and T. A. Buchanan. 1996. Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM. Diabetes 45: 1572–1579.
  • Bernal-Mizrachi, E., W. Wen, S. Stahlhut, C. M. Welling, and M. A. Permutt. 2001. Islet β cell expression of constitutively active Akt1/PKBα induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Investig. 108: 1631–1638.
  • Brown, K. K., B. R. Henke, S. G. Blanchard, J. E. Cobb, R. Mook, I. Kaldor, S. A. Kliewer, J. M. Lehmann, J. M. Lenhard, W. W. Harrington, P. J. Novak, W. Faison, J. G. Binz, M. A. Hashim, W. O. Oliver, H. R. Brown, D. J. Parks, K. D. Plunket, W. Q. Tong, J. A. Menius, K. Adkison, S. A. Noble, and T. M. Willson. 1999. A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes 48: 1415–1424.
  • Chung, D. C., S. B. Brown, F. Graeme-Cook, L. G. Tillotson, A. L. Warshaw, R. T. Jensen, and A. Arnold. 1998. Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors. Cancer Res. 58: 3706–3711.
  • Chung, D. C., A. P. Smith, D. N. Louis, F. Graeme-Cook, A. L. Warshaw, and A. Arnold. 1997. A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications. J. Clin. Investig. 100: 404–410.
  • Demetri, G. D., C. D. Fletcher, E. Mueller, P. Sarraf, R. Naujoks, N. Campbell, B. M. Spiegelman, and S. Singer. 1999. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA 96: 3951–3956.
  • Dubois, M., F. Pattou, J. Kerr-Conte, V. Gmyr, B. Vandewalle, P. Desreumaux, J. Auwerx, K. Schoonjans, and J. Lefebvre. 2000. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in normal human pancreatic islet cells. Diabetologia 43: 1165–1169.
  • Elnemr, A., T. Ohta, K. Iwata, I. Ninomia, S. Fushida, G. Nishimura, H. Kitagawa, M. Kayahara, M. Yamamoto, T. Terada, and K. Miwa. 2000. PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells. Int. J. Oncol. 17: 1157–1164.
  • Flier, S. N., R. N. Kulkarni, and C. R. Kahn. 2001. Evidence for a circulating islet cell growth factor in insulin-resistant states. Proc. Natl. Acad. Sci. USA 98: 7475–7480.
  • Gannon, M., C. Shiota, C. Postic, C. V. Wright, and M. Magnuson. 2000. Analysis of the Cre-mediated recombination driven by rat insulin promoter in embryonic and adult mouse pancreas. Genesis 26: 139–142.
  • Harbeck, M. C., D. C. Louie, J. Howland, B. A. Wolf, and P. L. Rothenberg. 1996. Expression of insulin receptor mRNA and insulin receptor substrate 1 in pancreatic islet beta-cells. Diabetes 45: 711–717.
  • Higa, M., Y.-T. Zhou, M. Ravazzola, D. Baetens, L. Orci, and R. H. Unger. 1999. Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats. Proc. Natl. Acad. Sci. USA 96: 11513–11518.
  • Ishihara, H., P. Maechler, A. Gjinovci, P. L. Herrera, and C. B. Wollheim. 2003. Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat. Cell Biol. 5: 330–335.
  • Josefsen, K., J. P. Stenvang, H. Kindmark, P. O. Berggren, T. Horn, T. Kjaer, and K. Buschard. 1996. Fluorescence-activated cell sorted rat islet cells and studies of the insulin secretory process. J. Endocrinol. 149: 145–154.
  • Kim, H. I., J. Y. Cha, S. Y. Kim, J. W. Kim, K. J. Roh, J. K. Seong, N. T. Lee, K. Y. Choi, K. S. Kim, and Y. H. Ahn. 2002. Peroxisomal proliferator-activated receptor-gamma upregulates glucokinase gene expression in beta-cells. Diabetes 51: 676–685.
  • Kim, H. I., J. W. Kim, S. H. Kim, J. Y. Cha, K. S. Kim, and Y. H. Ahn. 2000. Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter. Diabetes 49: 1517–1524.
  • Kubota, N., Y. Terauchi, H. Miki, H. Tamemoto, T. Yamauchi, K. Komeda, S. Satoh, R. Nakano, C. Ishii, T. Sugiyama, K. Eto, Y. Tsubamoto, A. Okuno, K. Murakami, H. Sekihara, G. Hasegawa, M. Naito, Y. Toyoshima, S. Tanaka, K. Shiota, T. Kitamura, T. Fujita, O. Ezaki, S. Aizawa, T. Kadowaki, et al. 1999. PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell 4: 597–609.
  • Kulkarni, R. N. 2002. Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function. Biochem. Soc. Trans. 30: 317–322.
  • Kulkarni, R. N., J. C. Bruning, J. N. Winnay, C. Postic, M. A. Magnuson, and C. R. Kahn. 1999. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96: 329–339.
  • Kulkarni, R. N., M. Holzenberger, D. Q. Shih, U. Ozcan, M. Stoffel, M. A. Magnuson, and C. R. Kahn. 2002. β-Cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter β-cell mass. Nat. Genet. 31: 111–115.
  • Kulkarni, R. N., and C. R. Kahn. 2000. Genetic models of insulin resistance: alterations in beta-cell biology, p. 299–323. In J. F. Habener and M. Hussain (ed.), Molecular basis of pancreas development and function. Kluwer Academic Publishers, New York, N.Y.
  • Kulkarni, R. N., J. N. Winnay, M. Daniels, J. C. Brüning, S. N. Flier, D. Hanahan, and C. R. Kahn. 1999. Altered function of insulin receptor substrate-1-deficient mouse islets and cultured β-cell lines. J. Clin. Investig. 104: R69–R75.
  • Michael, M. D., R. N. Kulkarni, C. Postic, S. F. Previs, G. I. Shulman, M. A. Magnuson, and C. R. Kahn. 2000. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell 6: 87–97.
  • Mueller, E., P. Sarraf, P. Tontonoz, R. M. Evans, K. J. Martin, M. Zhang, C. Fletcher, S. Singer, and B. M. Spiegelman. 1998. Terminal differentiation of human breast cancer through PPAR gamma. Mol. Cell 1: 465–470.
  • Mueller, E., M. Smith, P. Sarraf, T. Kroll, A. Aiyer, D. S. Kaufman, W. Oh, G. Demetri, W. D. Figg, X. P. Zhou, C. Eng, B. M. Spiegelman, and P. W. Kantoff. 2000. Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc. Natl. Acad. Sci. USA 97: 10990–10995.
  • Nikiforova, M. N., Y. E. Nikiforov, P. Biddinger, D. R. Gnepp, L. A. Grosembacher, B. L. Wajchenberg, J. A. Fagin, and R. M. Cohen. 1999. Frequent loss of heterozygosity at chromosome 3p14.2-3p21 in human pancreatic islet cell tumours. Clin. Endocrinol. 51: 27–33.
  • Rosen, E. D., C.-H. Hsu, X. Wang, S. Sakai, M. W. Freeman, F. J. Gonzalez, and B. M. Spiegelman. 2002. C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes Dev. 16: 22–26.
  • Rosen, E. D., and B. M. Spiegelman. 2001. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J. Biol. Chem. 276: 37731–37734.
  • Rumi, M. A., H. Sato, S. Ishihara, K. Kawashima, S. Hamamoto, H. Kazumori, T. Okuyama, R. Fukuda, N. Nagasue, and Y. Kinoshita. 2001. Peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma. Br. J. Cancer 84: 1640–1647.
  • Sarraf, P., E. Mueller, D. Jones, F. J. King, D. J. DeAngelo, J. B. Partridge, S. A. Holden, L. B. Chen, S. Singer, C. Fletcher, and B. M. Spiegelman. 1998. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat. Med. 4: 1046–1052.
  • Sarraf, P., E. Mueller, W. M. Smith, H. M. Wright, J. B. Kum, L. A. Aaltonen, A. de la Chapelle, B. M. Spiegelman, and C. Eng. 1999. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol. Cell 3: 799–804.
  • Shimabukuro, M., Y. T. Zhou, Y. Lee, and R. H. Unger. 1998. Troglitazone lowers islet fat and restores beta cell function of Zucker diabetic fatty rats. J. Biol. Chem. 273: 3547–3550.
  • Speel, E. J., J. Richter, H. Moch, C. Egenter, P. Saremaslani, K. Rutimann, J. Zhao, A. Barghorn, J. Roth, P. U. Heitz, and P. Komminoth. 1999. Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am. J. Pathol. 155: 1787–1794.
  • Tamemoto, H., T. Kadowaki, K. Tobe, T. Yagi, H. Sakura, T. Hayakawa, Y. Terauchi, K. Ueki, Y. Kaburagi, S. Satoh, et al. 1994. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372: 182–186.
  • Tontonoz, P., S. Singer, B. M. Forman, P. Sarraf, J. A. Fletcher, C. D. Fletcher, R. P. Brun, E. Mueller, S. Altiok, H. Oppenheim, R. M. Evans, and B. M. Spiegelman. 1997. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor. Proc. Natl. Acad. Sci. USA 94: 237–241.
  • Tsubouchi, Y., H. Sano, Y. Kawahito, S. Mukai, R. Yamada, M. Kohno, K. Inoue, T. Hla, and M. Kondo. 2000. Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis. Biochem. Biophys. Res. Commun. 270: 400–405.
  • Tuttle, R. L., N. S. Gill, W. Pugh, J. P. Lee, B. Koeberlein, E. E. Furth, K. S. Polonsky, A. Naji, and M. J. Birnbaum. 2001. Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat. Med. 7: 1133–1137.
  • Unger, R. H., and L. Orci. 2001. Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J. 15: 312–321.
  • Withers, D. J., J. S. Gutierrez, H. Towery, D. J. Burks, J. M. Ren, S. Previs, Y. Zhang, D. Bernal, S. Pons, G. I. Shulman, S. Bonner-Weir, and M. F. White. 1998. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391: 900–904.
  • Yang, C., T. J. Chang, J. C. Chang, M. W. Liu, T. Y. Tai, W. H. Hsu, and L. M. Chuang. 2001. Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway. Diabetes 50: 2598–2602.
  • Zhao, J., H. Moch, A. F. Scheidweiler, A. Baer, A. A. Schaffer, E. J. Speel, J. Roth, P. U. Heitz, and P. Komminoth. 2001. Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer 32: 364–372.
  • Zhou, Y. T., M. Shimabukuro, M. Y. Wang, Y. Lee, M. Higa, J. L. Milburn, C. B. Newgard, and R. H. Unger. 1998. Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells. Proc. Natl. Acad. Sci. USA 95: 8898–8903.

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