Diabetes and Metabolism Journal

  • 제42권6호
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  • Pages.465-471
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  • 2018
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  • 2233-6079(pISSN)
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  • 2233-6087(eISSN)
대한당뇨병학회 (Korean Diabetes Association)
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A Journey to Understand Glucose Homeostasis: Starting from Rat Glucose Transporter Type 2 Promoter Cloning to Hyperglycemia

  • Ahn, Yong Ho (Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine)
  • 투고 : 2018.07.30
  • 심사 : 2018.08.08
  • 발행 : 2018.12.30
⟨ 이전 논문 다음 논문 ⟩

초록

My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.

키워드

참고문헌

  1. Schuit FC, Huypens P, Heimberg H, Pipeleers DG. Glucose sensing in pancreatic beta-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. Diabetes 2001;50:1-11. https://doi.org/10.2337/diabetes.50.1.1
  2. Ahn YH, Kim JW, Han GS, Lee BG, Kim YS. Cloning and characterization of rat pancreatic beta-cell/liver type glucose transporter gene: a unique exon/intron organization. Arch Biochem Biophys 1995;323:387-96. https://doi.org/10.1006/abbi.1995.0059
  3. Kim JW, Ahn YH. CCAAT/enhancer binding protein regulates the promoter activity of the rat GLUT2 glucose transporter gene in liver cells. Biochem J 1998;336(Pt 1):83-90. https://doi.org/10.1042/bj3360083
  4. Cha JY, Kim H, Kim KS, Hur MW, Ahn Y. Identification of transacting factors responsible for the tissue-specific expression of human glucose transporter type 2 isoform gene. Cooperative role of hepatocyte nuclear factors 1alpha and 3beta. J Biol Chem 2000;275:18358-65. https://doi.org/10.1074/jbc.M909536199
  5. Cha JY, Kim HS, Kim HI, Im SS, Kim SY, Kim JW, Yeh BI, Ahn YH. Analysis of polymorphism of the GLUT2 promoter in NIDDM patients and its functional consequence to the promoter activity. Ann Clin Lab Sci 2002;32:114-22.
  6. 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. https://doi.org/10.1056/NEJM199411033311803
  7. Kim HI, Kim JW, Kim SH, Cha JY, Kim KS, Ahn YH. Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter. Diabetes 2000;49:1517-24. https://doi.org/10.2337/diabetes.49.9.1517
  8. Kim HI, Cha JY, Kim SY, Kim JW, Roh KJ, Seong JK, Lee NT, Choi KY, Kim KS, Ahn YH. Peroxisomal proliferator-activated receptor-gamma upregulates glucokinase gene expression in beta-cells. Diabetes 2002;51:676-85. https://doi.org/10.2337/diabetes.51.3.676
  9. Kim HI, Ahn YH. Role of peroxisome proliferator-activated receptor-gamma in the glucose-sensing apparatus of liver and beta-cells. Diabetes 2004;53 Suppl 1:S60-5. https://doi.org/10.2337/diabetes.53.2007.S60
  10. Kim SY, Kim HI, Park SK, Im SS, Li T, Cheon HG, Ahn YH. Liver glucokinase can be activated by peroxisome proliferator-activated receptor-gamma. Diabetes 2004;53 Suppl 1:S66-70. https://doi.org/10.2337/diabetes.53.2007.S66
  11. Kim TH, Kim H, Park JM, Im SS, Bae JS, Kim MY, Yoon HG, Cha JY, Kim KS, Ahn YH. Interrelationship between liver X receptor alpha, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma, and small heterodimer partner in the transcriptional regulation of glucokinase gene expression in liver. J Biol Chem 2009;284:15071-83. https://doi.org/10.1074/jbc.M109.006742
  12. Kim SY, Kim HI, Kim TH, Im SS, Park SK, Lee IK, Kim KS, Ahn YH. SREBP-1c mediates the insulin-dependent hepatic glucokinase expression. J Biol Chem 2004;279:30823-9. https://doi.org/10.1074/jbc.M313223200
  13. Im SS, Kang SY, Kim SY, Kim HI, Kim JW, Kim KS, Ahn YH. Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes. Diabetes 2005;54:1684-91. https://doi.org/10.2337/diabetes.54.6.1684
  14. Im SS, Kwon SK, Kang SY, Kim TH, Kim HI, Hur MW, Kim KS, Ahn YH. Regulation of GLUT4 gene expression by SREBP-1c in adipocytes. Biochem J 2006;399:131-9. https://doi.org/10.1042/BJ20060696
  15. Nakagawa Y, Shimano H, Yoshikawa T, Ide T, Tamura M, Furusawa M, Yamamoto T, Inoue N, Matsuzaka T, Takahashi A, Hasty AH, Suzuki H, Sone H, Toyoshima H, Yahagi N, Yamada N. TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes. Nat Med 2006;12: 107-13. https://doi.org/10.1038/nm1334
  16. Kim MY, Jo SH, Park JM, Kim TH, Im SS, Ahn YH. Adenovirus-mediated overexpression of Tcfe3 ameliorates hyperglycaemia in a mouse model of diabetes by upregulating glucokinase in the liver. Diabetologia 2013;56:635-43. https://doi.org/10.1007/s00125-012-2807-7
  17. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 1999;103: 1489-98. https://doi.org/10.1172/JCI6223
  18. Im SS, Kim MY, Kwon SK, Kim TH, Bae JS, Kim H, Kim KS, Oh GT, Ahn YH. Peroxisome proliferator-activated receptor {alpha} is responsible for the up-regulation of hepatic glucose-6-phosphatase gene expression in fasting and db/db mice. J Biol Chem 2011;286:1157-64. https://doi.org/10.1074/jbc.M110.157875
  19. Park JM, Kim MY, Kim TH, Min DK, Yang GE, Ahn YH. Prolactin regulatory element-binding (PREB) protein regulates hepatic glucose homeostasis. Biochim Biophys Acta 2018;1864 (6 Pt A):2097-107. https://doi.org/10.1016/j.bbadis.2018.03.024
  20. Niswender KD, Shiota M, Postic C, Cherrington AD, Magnuson MA. Effects of increased glucokinase gene copy number on glucose homeostasis and hepatic glucose metabolism. J Biol Chem 1997;272:22570-5. https://doi.org/10.1074/jbc.272.36.22570
  21. Park JM, Kim TH, Jo SH, Kim MY, Ahn YH. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity. Sci Rep 2015;5:17395. https://doi.org/10.1038/srep17395
  22. Park JM, Kim TH, Bae JS, Kim MY, Kim KS, Ahn YH. Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver. Biochem Biophys Res Commun 2010;403:329-34. https://doi.org/10.1016/j.bbrc.2010.11.028
  23. Jo SH, Kim MY, Park JM, Kim TH, Ahn YH. Txnip contributes to impaired glucose tolerance by upregulating the expression of genes involved in hepatic gluconeogenesis in mice. Diabetologia 2013;56:2723-32. https://doi.org/10.1007/s00125-013-3050-6
  24. Kim TH, Jo SH, Choi H, Park JM, Kim MY, Nojima H, Kim JW, Ahn YH. Identification of Creb3l4 as an essential negative regulator of adipogenesis. Cell Death Dis 2014;5:e1527. https://doi.org/10.1038/cddis.2014.490
  25. Kim TH, Park JM, Jo SH, Kim MY, Nojima H, Ahn YH. Effects of low-fat diet and aging on metabolic profiles of Creb3l4 knockout mice. Nutr Diabetes 2015;5:e179. https://doi.org/10.1038/nutd.2015.29
  26. Kim TH, Park JM, Kim MY, Ahn YH. The role of CREB3L4 in the proliferation of prostate cancer cells. Sci Rep 2017;7:45300. https://doi.org/10.1038/srep45300

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