본문 바로가기
KERD
논문KCI 등재

CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis

2

조회

0

다운로드

5

인용

0

참고문헌

키워드

주제분류화학

초록

Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed.

Abstract

Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed.

참고문헌 (86)

  1. Nordlie, R. C., "Regulation of glucose production by the liver", Annu. Rev. Nutr, 19, pp.379~406 (1999)
  2. Pilkis, S. J., "Hormonal regulation of hepatic gluconeogenesis and glycolysis", Annu. Rev. Biochem, 57, pp.755~783 (1988)
  3. Pilkis, S. J., "Hepatic gluconeogenesis", glycolysis: regulation and structure, Annu. Rev. Nutr, pp.1991, 11[DOI]
  4. Towle, H. C., "Regulation of the expression of lipogenic enzyme genes by carbohydrate", Annu. Rev. Nutr, 17, pp.405~433 (1997)
  5. Brown, M. S., "Selective versus total insulin resistance: a pathogenic paradox", Cell Metab, 7, pp.95~96 (2008)
  6. Postic, C., "ChREBP, a transcriptional regulator of glucose and lipid metabolism", Annu. Rev. Nutr, 27, pp.179~192 (2007)
  7. Uyeda, K., "Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis", Cell Metab, 4, pp.107~110 (2006)
  8. Moore, M. C., "Autoregulation of hepatic glucose production", Eur. J. Endocrinol, 138, pp.240~248 (1998)
  9. Saltiel, A. R., "Insulin signalling and the regulation of glucose and lipid metabolism", Nature, 414, pp.799~806 (2001)
  10. Herzig, S., "CREB regulates hepatic gluconeogenesis through the coactivator PGC-1", Nature, 413, pp.179~183 (2001)
  11. Kim, D. K., "Orphan nuclear receptor estrogen-related receptor gamma (ERRgamma) is key regulator of hepatic gluconeogenesis", J. Biol. Chem, 287, pp.21628~21639 (2012)
  12. Lee, M. W., "Regulation of hepatic gluconeogenesis by an ER-bound transcription factor, CREBH", Cell Metab, 11, pp.331~339 (2010)
  13. van Schaftingen, E., "The glucose-6- phosphatase system", Biochem. J, 362, pp.513~532 (2002)
  14. Bedford, D. C., "Disrupting the CH1 domain structure in the acetyltransferases CBP and p300 results in lean mice with increased metabolic control", Cell Metab, 14, pp.219~230 (2011)
  15. Choi, D., "Protein arginine methyltransferase 1 regulates hepatic glucose production in a FoxO1-dependent manner", Hepatology, 56, pp.1546~1556 (2012)
  16. Koo, S. H., "The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism", Nature, 437, pp.1109~1111 (2005)
  17. Krones-Herzig, A., "Signal-dependent control of gluconeogenic key enzyme genes through coactivator-associated arginine methyltransferase 1", J. Biol. Chem, 281, pp.3025~3029 (2006)
  18. Puigserver, P., "Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction", Nature, 423, pp.550~555 (2003)
  19. Yoon, J. C., "Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1", Nature, 413, pp.131~138 (2001)
  20. Lee, J. M., "AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB.CRTC2 complex by orphan nuclear receptor small heterodimer partner", J. Biol. Chem, 285, pp.32182~32191 (2010)
  21. Nedumaran, B., "DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression", J. Biol. Chem, 284, pp.27511~27523 (2009)
  22. Oh, K. J., "TCF7L2 modulates glucose homeostasis by regulating CREB-and FoxO1-dependent transcriptional pathway in the liver.", PloS. Genetics, 8, pp.e1002986~ (2012)
  23. Gonzalez, G. A., "Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133", Cell, 59, pp.675~680 (1989)
  24. Arias, J., "Activation of cAMP and mitogen responsive genes relies on a common nuclear factor", Nature, 370, pp.226~229 (1994)
  25. Chrivia, J. C., "Phosphorylated CREB binds specifically to the nuclear protein CBP", Nature, 365, pp.855~859 (1993)
  26. Kwok, R. P., "Nuclear protein CBP is a coactivator for the transcription factor CREB", Nature, 370, pp.223~226 (1994)
  27. Conkright, M. D., "Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness", Mol. Cell, 11, pp.1101~1108 (2003)
  28. Iourgenko, V., "Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells", Proc. Natl. Acad. Sci. U. S. A, 100, pp.12147~12152 (2003)
  29. Alberts, A. S., "Recombinant cyclic AMP response element binding protein (CREB) phosphorylated on Ser-133 is transcriptionally active upon its introduction into fibroblast nuclei", J. Biol. Chem, 269, pp.7623~7630 (1994)
  30. Wadzinski, B. E., "Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation", Mol. Cell. Biol, 13, pp.2822~2834 (1993)
  31. Hanson, R. W., "Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression", Annu. Rev. Biochem, 66, pp.581~611 (1997)
  32. Erion, D. M., "Prevention of hepatic steatosis and hepatic insulin resistance by knockdown of cAMP response element-binding protein", Cell Metab, 10, pp.499~506 (2009)
  33. Bannister, A. J, "The CBP co-activator is a histone acetyltransferase", Nature, 384, pp.641~643 (1996)
  34. Ogryzko, V. V., "The transcriptional coactivators p300 and CBP are histone acetyltransferases", Cell, 87, pp.953~959 (1996)
  35. Tanaka, Y., "Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome", Proc. Natl. Acad. Sci. U. S. A, 94, pp.10215~10220 (1997)
  36. Yao, T. P., "Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300", Cell, 93, pp.361~372 (1998)
  37. Yamauchi, T., "Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice", Nat. Genet, 30, pp.221~226 (2002)
  38. He, L., "Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein", Cell, 137, pp.635~646 (2009)
  39. Dentin, R., "Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver", Biochimie, 87, pp.81~86 (2005)
  40. Altarejos, J. Y., "CREB and the CRTC co-activators: sensors for hormonal and metabolic signals", Nat. Rev. Mol. Cell Biol, 12, pp.141~151 (2011)
  41. Yoon, Y. S., "Suppressor of MEK null (SMEK)", protein phosphatase 4 catalytic subunit (PP4C) is a key regulator of hepatic gluconeogenesis, 2010, pp.107, 17704~17709
  42. Wang, Y., "Inositol-1, 4, 5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes", Nature, 485, pp.128~132 (2012)
  43. Young-Sil Yoon, "Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis", Experimental and Molecular Medicine, 41(8), pp.577~583 (2009), 생화학분자생물학회
  44. Saberi, M., "Novel liver-specific TORC2 siRNA corrects hyperglycemia in rodent models of type 2 diabetes", Am. J. Physiol. Endocrinol. Metab, 297, pp.E1137~E1146 (2009)
  45. Wang, Y., "Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity", Proc. Natl. Acad. Sci. U. S. A, 107, pp.3087~3092 (2010)
  46. Wang, Y., "The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis", Nature, 460, pp.534~537 (2009)
  47. Ryu, D., "TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1", Cell Metab, 9, pp.240~251 (2009)
  48. Accili, D, "FoxOs at the crossroads of cellular metabolism, differentiation, and transformation", Cell, 117, pp.421~426 (2004)
  49. Barthel, A., "FoxO proteins in insulin action and metabolism", Trends Endocrinol. Metab, 16, pp.183~189 (2005)
  50. Biggs, W. H.3rd,, "Protein kinase B", Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1, 1999, pp.96, 7421~7426
  51. Brunet, A., "Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor", Cell, 96, pp.857~868 (1999)
  52. Nakae, J., "Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway", J. Biol. Chem, 274, pp.15982~15985 (1999)
  53. Daitoku, H., "Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity", Proc. Natl. Acad. Sci. U. S. A, 101, pp.10042~10047 (2004)
  54. Motta, M. C., "Mammalian SIRT1 represses forkhead transcription factors", Cell, 116, pp.551~563 (2004)
  55. van der Horst, A., "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)", J. Biol. Chem, 279, pp.28873~28879 (2004)
  56. Haeusler, R. A., "FoxOs function synergistically to promote glucose production", J. Biol. Chem, 285, pp.35245~35248 (2010)
  57. Ayala, J. E., "Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence", Diabetes, 48, pp.1885~1889 (1999)
  58. Matsumoto, M., "Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver", Cell Metab, 6, pp.208~216 (2007)
  59. Kim, D. H., "FoxO6 integrates insulin signaling with gluconeogenesis in the liver", Diabetes, 60, pp.2763~2774 (2011)
  60. Puigserver, P., "A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis", Cell, 92, pp.829~839 (1998)
  61. Puigserver, P., "Activation of PPARgamma coactivator-1 through transcription factor docking", Science, 286, pp.1368~1371 (1999)
  62. Wallberg, A. E., "Coordination of p300-mediated chromatin remodeling and TRAP", mediator function through coactivator PGC-1alpha, 2003, pp.12, 1137~1149
  63. Lin, J., "Metabolic control through the PGC-1 family of transcription coactivators", Cell. Metab, 1, pp.361~370 (2005)
  64. Ze-Min Huang, "Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells", BMB Reports, 45(6), pp.331~336 (2012), 생화학분자생물학회[DOI]
  65. Koo, S. H., "PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3", Nat. Med, 10, pp.530~534 (2004)
  66. Lin, J., "Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice", Cell 119, 119, pp.121~135 (2004)
  67. Choi, D., "Protein arginine methylation in hepatic glucose metabolism regulation: Histone or nonhistone? That is the question. Reply", Hepatology, 57, pp.2091~ (2013)
  68. Takahashi, Y., "Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16", Cell Metab, 13, pp.505~516 (2011)
  69. Yamagata, K., "Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt", Mol. Cell, 32, pp.221~231 (2008)
  70. Iyer, A. K., "Molecular mechanisms of DAX1 action", Mol. Genet. Metab, 83, pp.60~73 (2004)
  71. Seol, W., "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors", Science, 272, pp.1336~1339 (1996)
  72. Chanda, D., "Molecular basis of endocrine regulation by orphan nuclear receptor Small Heterodimer Partner", Endocr. J, 55, pp.253~268 (2008)
  73. Lee, Y. S., "Structure and function of the atypical orphan nuclear receptor small heterodimer partner", Int. Rev. Cytol, 261, pp.117~158 (2007)
  74. Kim, Y. D., "Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP", Diabetes, 57, pp.306~314 (2008)
  75. Behrens, J., "Functional interaction of beta-catenin with the transcription factor LEF-1", Nature, 382, pp.638~642 (1996)
  76. Huber, O., "Nuclear localization of beta-catenin by interaction with transcription factor LEF-1.", Mech. Dev, 59, pp.3~10 (1996)
  77. Molenaar, M., "XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos", Cell, 86, pp.391~399 (1996)
  78. Rubinfeld, B., "Stabilization of beta-catenin by genetic defects in melanoma cell lines", Science, 275, pp.1790~1792 (1997)
  79. Clevers, H., "Wnt", beta-catenin signaling in development and disease, 2006, pp.127, 469~480
  80. Chandak, G. R., "Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population", Diabetologia, 50, pp.63~67 (2007)
  81. Grant, S. F., "Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes", Nat. Genet, 38, pp.320~323 (2006)
  82. Hayashi, T., "Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population", Diabetologia, 50, pp.980~984 (2007)
  83. Helgason, A., "Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution", Nat. Genet, 39, pp.218~225 (2007)
  84. Lehman, D. M., "Haplotypes of transcription factor 7-like 2(TCF7L2)gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans", Diabetes, 56, pp.389~393 (2007)
  85. Yi, F., "TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase- 3beta", J. Biol. Chem, 280, pp.1457~1464 (2005)
  86. Norton, L., "Chromatin occupancy of transcription factor 7-like 2(TCF7L2)and its role in hepatic glucose metabolism", Diabetologia, 54, pp.3132~3142 (2011)

관련 논문AI추천

MiR-542-5p Inhibits Hyperglycemia and Hyperlipoidemia by Targeting FOXO1 in the LiverBo-Ning Cheng, Fang Tian, Hui-Min Ying, Juan Chen, Yuan-Yuan Wang연세대학교의과대학 · Yonsei Medical Journal2020 · 제61권 제9호The molecular mechanism of propionate-regulating gluconeogenesis in bovine hepatocytesHuang Li, Li Yu, Mao Tiantian, Pang Rui, Xiao Xiao, Xu Wei, Yu Jiajia, Zhu Wen아세아·태평양축산학회 · Animal Bioscience2023 · 제36권 제11호Enhancement of the SESN2-SHP cascade by melatonin ameliorates hepatic gluconeogenesis by inhibiting the CRBN-BTG2-CREBH signaling pathwayAn Seungwon, Djalilian Ali R., Harris Robert A., Joo Dong Jin, Kim Yong Deuk, Koh Hong, Lee Hyungjo, Nedumaran Balachandar, Park Chul-Seung, Shin Keong Sub생화학분자생물학회 · Experimental and Molecular Medicine2023 · 제55권 Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver diseaseEiji Kakazu, Masaaki Mino, Tatsuya Kanto대한간학회 · Clinical and Molecular Hepatology2025 · 제31권 제3호Hepatic transcriptional changes in critical genes for gluconeogenesis following castration of bulls백명기, dilla mareistia fassah, Jin Young Jeong아세아·태평양축산학회 · Animal Bioscience2018 · 제31권 제4호Emerging roles of PHLPP phosphatases in metabolism오아름, Jong-Ho Cha, KyeongJin Kim, Sang Bae Lee, Soon-Sun Hong, Yelin Jeong생화학분자생물학회 · BMB Reports2021 · 제54권 제9호

이 간행물의 다른 논문 (8건)