Pérez-Mendoza M, De Ita-Pérez D, Díaz-Muñoz M

Language: Spanish
References: 17
Page: 10-20
PDF size: 592.25 Kb.

ABSTRACT

Gluconeogenesis (GNG) is a metabolic pathway that allows the generation of glucose from non-glycosidic substrates such as amino acids, lactate and glycerol. GNG appeared very early in the phylogenetic development of living beings. In vertebrates it is active during fasting, and inhibited after feeding. The two principal enzymes of the process, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, are regulated for a complex network of endocrine and transcriptional factors. GNG is also modulated by the circadian molecular clock which communicates 24-h rhythmicity to the process. Within the liver, GNG is more active in periportal than pericentral hepatocytes. Several diseases, such as diabetes, show deregulation of the GNG.

REFERENCES

1. Nuttall FQ, Ngo A, Gannon MC (2008) Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant? Diabetes Metab Res Rev 24:438-458.

2. Fuchs G (2011) Alternative pathways of carbon dioxide fixation: insights into the early evolution of life? Annu Rev Microbiol 65:631-658.

3. Chakravarty K, Cassuto H, Reshef L, Hanson RW (2005) Factors that control the tissue-specific transcription of the gene for phosphoenolpyruvate carboxykinase-c. Crit Rev Biochem Mol Biol 40:129–154.

4. Chakravarty K, Hanson RW (2008) Insulin regulation of phosphoenolpyruvate carboxykinase-C gene transcription: The Role of Sterol Regulatory Element-Binding Protein 1c. Nut Rev 65:S47-S56.

5. Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC, Hirota T, Nusinow DA, Sun X, Landais S, Kodama Y, Brenner DA, Montminy M, Kay SA (2010) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med 16:1152–1156.

6. Yin L, Wu N, Lazar MA (2010) Nuclear receptor Rev-erbα: a heme receptor that coordinates circadian rhythm and metabolism. NRS 8:1-6.

7. Yabaluri N, Bashyam MD (2010) Hormonal regulation of gluconeogenic gene transcripcion in the liver. J Biosci 35:473-484.

8. Xu C, Chakravarty K, Kong X, Tuy TT, Arinze IJ, Bone F, Massillon D (2007) Several transcription factors are recruited to the glucose-6-phosphatase gene promoter in response to palmitate in rat hepatocytes and H4IIE cells. J Nutr 137:554–559.

9. Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330:1349-1354.

10. Kennaway DJ, Owens JA, Voultsios A, Boden MJ, Varcoe TJ (2007) Metabolic homeostasis in mice with disrupted Clock gene expression in peripheral tissues. Am J Physiol Regul Integr Comp Physiol 293:1528-1537.

11. Hatori M, Panda S (2010) CRY links the circadian clock and CREB-mediated gluconeogenesis. Cell Res 20:1285-1288.

12. Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14(23):2950-61.

13. Katz NR (1992) Metabolic heterogeneity of hepatocytes across the liver acinus. J Nutr 122:843-849.

14. Rajas F, Jourdan-Pineau H, Stefanutti A, Mrad EA, Iynedjian PB, Mithieux G. (2007) Immunocytochemical localization of glucose 6-phosphatase and cytosolic phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected metabolic zonation. Histochem Cell Biol 127(5):567.

15. Burke ZD, Tosh D (2006) The Wnt/β-catenin pathway: master regulador of liver zonation? BioEssays 28:1072-1077.

16. Hanson RW, Reshef L (1997) Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annu Rev Biochem 66:581-611.

17. Choudhury M, Qadri I, Rahman SM, Schroeder-Gloeckler J, Janssen RC, Friedman JE (2011) C/EBPβ is a AMP kinase sensitive and up-regulates PEPCK in response to ER stress in hepatoma cells. Mol Cell Endocrinol 331:102-108.