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Signal Transduction

Phosphoinositide 3-Kinase Catalytic Subunit Deletion and Regulatory Subunit Deletion Have Opposite Effects on Insulin Sensitivity in Mice

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Pages 1596-1607 | Received 24 Jul 2004, Accepted 29 Nov 2004, Published online: 27 Mar 2023

REFERENCES

  • Aguirre, V., T. Uchida, L. Yenush, R. Davis, and M. F. White. 2000. The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J. Biol. Chem. 275:9047–9054.
  • Aguirre, V., E. D. Werner, J. Giraud, Y. H. Lee, S. E. Shoelson, and M. F. White. 2002. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J. Biol. Chem. 277:1531–1537.
  • Asano, T., A. Kanda, H. Katagiri, M. Nawano, T. Ogihara, K. Inukai, M. Anai, Y. Fukushima, Y. Yazaki, M. Kikuchi, R. Hooshmand-Rad, C. H. Heldin, Y. Oka, and M. Funaki. 2000. p110α is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity. J. Biol. Chem. 275:17671–17676.
  • Barbour, L. A., J. Shao, L. Qiao, W. Leitner, M. Anderson, J. E. Friedman, and B. Draznin. 2004. Human placental growth hormone increases expression of the p85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle. Endocrinology 145:1144–1150.
  • Barroso, I., J. Luan, R. P. Middelberg, A. H. Harding, P. W. Franks, R. W. Jakes, D. Clayton, A. J. Schafer, S. O'Rahilly, and N. J. Wareham. 2003. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol. 1:E20.
  • Bi, L., I. Okabe, D. J. Bernard, and R. L. Nussbaum. 2002. Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase. Mamm. Genome 13:169–172.
  • Bi, L., I. Okabe, D. J. Bernard, A. Wynshaw-Boris, and R. L. Nussbaum. 1999. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase. J. Biol. Chem. 274:10963–10968.
  • Bruning, J. C., J. Winnay, S. Bonner-Weir, S. I. Taylor, D. Accili, and C. R. Kahn. 1997. Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88:561–572.
  • Carpenter, C. L., B. C. Duckworth, K. R. Auger, B. Cohen, B. S. Schaffhausen, and L. C. Cantley. 1990. Purification and characterization of phosphoinositide 3-kinase from rat liver. J. Biol. Chem. 265:19704–19711.
  • Cheatham, B., C. J. Vlahos, L. Cheatham, L. Wang, J. Blenis, and C. R. Kahn. 1994. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14:4902–4911.
  • Chen, D., F. Mauvais-Jarvis, M. Bluher, S. J. Fisher, A. Jozsi, L. J. Goodyear, K. Ueki, and C. R. Kahn. 2004. p50α/p55α phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity. Mol. Cell. Biol. 24:320–329.
  • Cho, H., J. Mu, J. K. Kim, J. L. Thorvaldsen, Q. Chu, E. B. Crenshaw III, K. H. Kaestner, M. S. Bartolomei, G. I. Shulman, and M. J. Birnbaum. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292:1728–1731.
  • Cong, L. N., H. Chen, Y. Li, L. Zhou, M. A. McGibbon, S. I. Taylor, and M. J. Quon. 1997. Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. Mol. Endocrinol. 11:1881–1890.
  • Devroe, E., and P. A. Silver. 2002. Retrovirus-delivered siRNA. BMC Biotechnol. 2:15.
  • Fruman, D. A., F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley. 2000. Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat. Genet. 26:379–382.
  • Fruman, D. A., R. E. Meyers, and L. C. Cantley. 1998. Phosphoinositide kinases. Annu. Rev. Biochem. 67:481–507.
  • Fruman, D. A., S. B. Snapper, C. M. Yballe, L. Davidson, J. Y. Yu, F. W. Alt, and L. C. Cantley. 1999. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α. Science 283:393–397.
  • Gao, Z., D. Hwang, F. Bataille, M. Lefevre, D. York, M. J. Quon, and J. Ye. 2002. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J. Biol. Chem. 277:48115–48121.
  • Garofalo, R. S., S. J. Orena, K. Rafidi, A. J. Torchia, J. L. Stock, A. L. Hildebrandt, T. Coskran, S. C. Black, D. J. Brees, J. R. Wicks, J. D. McNeish, and K. G. Coleman. 2003. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Investig. 112:197–208.
  • George, S., J. J. Rochford, C. Wolfrum, S. L. Gray, S. Schinner, J. C. Wilson, M. A. Soos, P. R. Murgatroyd, R. M. Williams, C. L. Acerini, D. B. Dunger, D. Barford, A. M. Umpleby, N. J. Wareham, H. A. Davies, A. J. Schafer, M. Stoffel, S. O'Rahilly, and I. Barroso. 2004. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science 304:1325–1328.
  • Goldstein, B. J. 2002. Insulin resistance as the core defect in type 2 diabetes mellitus. Am. J. Cardiol. 90:3G–10G.
  • Greene, M. W., H. Sakaue, L. Wang, D. R. Alessi, and R. A. Roth. 2003. Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by serine 312 phosphorylation. J. Biol. Chem. 278:8199–8211.
  • Gual, P., T. Gremeaux, T. Gonzalez, Y. Le Marchand-Brustel, and J. F. Tanti. 2003. MAP kinases and mTOR mediate insulin-induced phosphorylation of insulin receptor substrate-1 on serine residues 307, 612 and 632. Diabetologia 46:1532–1542.
  • Gupta, N., A. M. Scharenberg, D. A. Fruman, L. C. Cantley, J. P. Kinet, and E. O. Long. 1999. The SH2 domain-containing inositol 5′-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during FcgammaRIIb1-mediated inhibition of B cell receptor signaling. J. Biol. Chem. 274:7489–7494.
  • Hara, K., K. Yonezawa, H. Sakaue, A. Ando, K. Kotani, T. Kitamura, Y. Kitamura, H. Ueda, L. Stephens, T. R. Jackson, et al. 1994. 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells. Proc. Natl. Acad. Sci. USA 91:7415–7419.
  • Hirosumi, J., G. Tuncman, L. Chang, C. Z. Gorgun, K. T. Uysal, K. Maeda, M. Karin, and G. S. Hotamisligil. 2002. A central role for JNK in obesity and insulin resistance. Nature 420:333–336.
  • Hotamisligil, G. S., N. S. Shargill, and B. M. Spiegelman. 1993. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91.
  • Katome, T., T. Obata, R. Matsushima, N. Masuyama, L. C. Cantley, Y. Gotoh, K. Kishi, H. Shiota, and Y. Ebina. 2003. Use of RNA interference-mediated gene silencing and adenoviral overexpression to elucidate the roles of AKT/protein kinase B isoforms in insulin actions. J. Biol. Chem. 278:28312–28323.
  • Kirwan, J. P., A. Varastehpour, M. Jing, L. Presley, J. Shao, J. E. Friedman, and P. M. Catalano. 2004. Reversal of insulin resistance postpartum is linked to enhanced skeletal muscle insulin signaling. J. Clin. Endocrinol. Metab. 89:4678–4684.
  • Kotani, K., A. J. Carozzi, H. Sakaue, K. Hara, L. J. Robinson, S. F. Clark, K. Yonezawa, D. E. James, and M. Kasuga. 1995. Requirement for phosphoinositide 3-kinase in insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 209:343–348.
  • Li, J., K. DeFea, and R. A. Roth. 1999. Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 274:9351–9356.
  • Liu, Y. F., K. Paz, A. Herschkovitz, A. Alt, T. Tennenbaum, S. R. Sampson, M. Ohba, T. Kuroki, D. LeRoith, and Y. Zick. 2001. Insulin stimulates PKCζ-mediated phosphorylation of insulin receptor substrate-1 (IRS-1). A self-attenuated mechanism to negatively regulate the function of IRS proteins. J. Biol. Chem. 276:14459–14465.
  • Mauvais-Jarvis, F., K. Ueki, D. A. Fruman, M. F. Hirshman, K. Sakamoto, L. J. Goodyear, M. Iannacone, D. Accili, L. C. Cantley, and C. R. Kahn. 2002. Reduced expression of the murine p85α subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J. Clin. Investig. 109:141–149.
  • O'Connor, J. C., and G. G. Freund. 2003. Vanadate and rapamycin synergistically enhance insulin-stimulated glucose uptake. Metabolism 52:666–674.
  • Okada, T., Y. Kawano, T. Sakakibara, O. Hazeki, and M. Ui. 1994. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J. Biol. Chem. 269:3568–3573.
  • Ozes, O. N., H. Akca, L. D. Mayo, J. A. Gustin, T. Maehama, J. E. Dixon, and D. B. Donner. 2001. A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc. Natl. Acad. Sci. USA 98:4640–4645.
  • Pirola, L., S. Bonnafous, A. M. Johnston, C. Chaussade, F. Portis, and E. Van Obberghen. 2003. Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. J. Biol. Chem. 278:15641–15651.
  • Quon, M. J., H. Chen, B. L. Ing, M.-L. Liu, M. J. Zarnowski, K. Yonezawa, K. M., S. W. Cushman, and S. I. Taylor. 1995. Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of GLUT 4 in transfected rat adipose cells. Mol. Cell. Biol. 15:5403–5411.
  • Terauchi, Y., Y. Tsuji, S. Satoh, H. Minoura, K. Murakami, A. Okuno, K. Inukai, T. Asano, Y. Kaburagi, K. Ueki, H. Nakajima, T. Hanafusa, Y. Matsuzawa, H. Sekihara, Y. Yin, J. C. Barrett, H. Oda, T. Ishikawa, Y. Akanuma, I. Komuro, M. Suzuki, K. Yamamura, T. Kodama, H. Suzuki, T. Kadowaki, et al. 1999. Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat. Genet. 21:230–235.
  • Ueki, K., P. Algenstaedt, F. Mauvais-Jarvis, and C. R. Kahn. 2000. Positive and negative regulation of phosphoinositide 3-kinase-dependent signaling pathways by three different gene products of the p85α regulatory subunit. Mol. Cell. Biol. 20:8035–8046.
  • Ueki, K., D. A. Fruman, S. M. Brachmann, Y. H. Tseng, L. C. Cantley, and C. R. Kahn. 2002. Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. Mol. Cell. Biol. 22:965–977.
  • Ueki, K., D. A. Fruman, C. M. Yballe, M. Fasshauer, J. Klein, T. Asano, L. C. Cantley, and C. R. Kahn. 2003. Positive and negative roles of p85α and p85β regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J. Biol. Chem. 278:48453–48466.
  • Ueki, K., C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, and L. C. Cantley. 2002. Increased insulin sensitivity in mice lacking p85β subunit of phosphoinositide 3-kinase. Proc. Natl. Acad. Sci. USA 99:419–424.
  • Um, S. H., F. Frigerio, M. Watanabe, F. Picard, M. Joaquin, M. Sticker, S. Fumagalli, P. R. Allegrini, S. C. Kozma, J. Auwerx, and G. Thomas. 2004. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431:200–205.
  • Uysal, K. T., S. M. Wiesbrock, M. W. Marino, and G. S. Hotamisligil. 1997. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614.
  • Yu, J., Y. Zhang, J. McIlroy, T. Rordorf-Nikolic, G. A. Orr, and J. M. Backer. 1998. Regulation of the p85/p110 phosphatidylinositol 3′-kinase: stabilization and inhibition of the p110α catalytic subunit by the p85 regulatory subunit. Mol. Cell. Biol. 18:1379–1387.
  • Zick, Y. 2001. Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol. 11:437–441.

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