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Transcriptional regulation of liver phosphoenolpyruvate carboxykinase by biotin in diabetic rats

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Abstract

Rat liver phosphoenolpyruvate carboxykinase (PEPCK) activity was followed over a time period of 5h following administration of biotin to streptozotocin-induced diabetic rats. In parallel with the decrease in enzyme activity liver PEPCK mRNA decreased by 85% at 3 h after injection of biotin to diabetic rats. There was no significant change in the accumulation of kidney PEPCK mRNA. Parallel studies with insulin indicated that biotin had a regulatory effect similar to that of insulin on liver PEPCK mRNA. The administration of biotin did not change the insulin status of the diabetic rat indicating that biotin did not act via insulin. The transcriptional activity of the hepatic PEPCK gene, as measured by nuclear run-on assay, was decreased by 57% within 30 min of biotin administration. The results suggest that biotin regulates hepatic, but not renal, PEPCK mRNA concentration at the transcriptional level in diabetic rats.

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References

  1. 1.

    Granner DK, Pilkis S: The genes of hepatic glucose metabolism. J Biol Chem 265:10173–10176, 1990

  2. 2.

    O'Brien RM, Granner DK: Regulation of gene expression by insulin. Biochem J 278:609–619, 1991

  3. 3.

    O'Brien RM, Lucas PC, Yamasaki T, Bonovich MT, Forest CD, Granner DK: Insulin and phorbol esters act through the same DNA element to inhibit phosphoenolpyruvate carboxykinase gene transcription. Biochem Soc Trans 20:686–690, 1992

  4. 4.

    Granner DK, Andreone T, Sasaki K, Beale E: Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulin. Nature 305:549–551, 1983

  5. 5.

    Sasaki K, Cripe TP, Koch SR, Andreone TL, Peterson DD, Beale EG, Granner DK: Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. J Biol Chem 259:15242–15251, 1984

  6. 6.

    Bokar JA, Roesler WJ, Vandenbark GR, Kaetzel DM, Hanson RW, Nilson JH: Characterization of the cAMP responsive elements from the genes for the α-subunit of glycoprotein hormones and phosphoenolpyruvate carboxykinase (GTP). J Biol Chem 263:19740–19747, 1988

  7. 7.

    Andreone TL, Beale EG, Bar RS, Granner DK: Insulin decreases phosphoenolpyruvate carboxykinase (GTP) mRNA activity by a receptor-mediated process. J Biol Chem 257:35–38, 1982

  8. 8.

    Peterson DD, Koch SR, Graner DK: 3′ noncoding region of phosphoenolpyruvate carboxykinase mRNA contains a glucocorticoid-responsive mRNA-stabilizing element. Proc Natl Acad Sci USA 86:7800–7804, 1989

  9. 9.

    Loose DC, Cameron DK, Short HP, Hanson RW: Thyroid hormone regulates transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase (GTP) in rat liver. Biochemistry 24: 4509–4512, 1985

  10. 10.

    Giralt M, Park EA, Gurney AL, Liu J, Hakimi P, Hanson RW: Identification of a thyroid hormone response element in the phosphoenolpyruvate carboxykinase (GTP) gene. Evidence for synergistic interaction between thyroid hormone and cAMP cis-regulatory elements. J Biol Chem 266:21991–21996, 1991

  11. 11.

    Rosa JL, Bartrons R, Touler A: Gene expression of regulatory enzymes of glycolysis/gluconeogenesis in regenerating rat liver. Biochem J 287:113–116, 1992

  12. 12.

    Zabala MT, Lorenzo P, Alvarez L, Berlanga JJ, Garcia-Ruiz JP: Serotonin increases the cAMP concentration and the phosphoenolpyruvate carboxykinase mRNA in rat kidney, small intestine and liver. J Cell Physiol 150:451–455, 1992

  13. 13.

    Hill MR, McCallum RE: Identification of tumor necrosis factor as a transcriptional regulator of the phosphoenolpyruvate carboxykinase gene following endotoxin treatment of mice. Infection and Immunity 60:4040–4050, 1992

  14. 14.

    Lucas PC, O'Brien RM, Mitchell JA, Davis CM, Imai E, Forman BM, Samuals HH, Granner DK: A retinoic acid responsive element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. Proc Natl Acad Sci USA 88:2184–2188, 1991

  15. 15.

    Iynedjian PB, Gjinovci A, Renold AE: Stimulation by insulin of glucokinase gene transcription in livers of diabetic rats. J Biol Chem 263:740–744, 1988

  16. 16.

    Andreone TL, Printz RL, Pilkis SJ, Magnuson MA, Granner DK: The aminoacid sequence of rat liver glucokinase deduced from cloned cDNA. J Biol Chem 264:363–369, 1989

  17. 17.

    Chauhan J, Dakshinamurti K: Transcriptional regulation of the glucokinase gene by biotin in starved rats. J Biol Chem 266: 10035–10038, 1991

  18. 18.

    Dakshinamurti K, Cheah-Tan C: Biotin-mediated synthesis of hepatic glucokinase in the rat. Arch Biochem Biophys 127:17–21, 1968

  19. 19.

    Petrescu I, Bojan O, Saied M, Barzu O, Schmidt F, Kuhnle HF: Determination of phosphoenolpyruvate carboxykinase activity with deoxyguanosine 5′-diphosphate as nucleotide substrate. Anal Biochem 96:279–281, 1979

  20. 20.

    Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976

  21. 21.

    Chomczynski P, Sacchi N: Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987

  22. 22.

    Watford M, Mapes RE: Hormonal and acid-base regulation of phosphoenolpyruvate carboxykinase mRNA levels in rat kidney. Arch Biochem Biophys 282:399–403, 1990

  23. 23.

    Iynedjian PB, Ballard FJ, Hanson RW: The regulation of phosphoenolpyruvate carboxykinase (GTP) synthesis in rat kidney cortex. J Biol Chem 250:5596–5603, 1975

  24. 24.

    Cimbala MA, Lamers WH, Nelson K, Monahan JE, Warren HY, Hanson RW: Rapid changes in the concentration of phosphoenolpyruvate carboxykinase mRNA in rat liver and kidney. J Biol Chem 257:7629–7636, 1982

  25. 25.

    O'Brien RM, Lucas PC, Forest CD, Magnuson MA, Granner DK: Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. Science 249:533–537, 1990

  26. 26.

    Phillippe J: Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element. Proc Natl Acad Sci USA 88: 7224–7227, 1991.

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Correspondence to Krishnamurti Dakshinamurti.

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Dakshinamurti, K., Li, W. Transcriptional regulation of liver phosphoenolpyruvate carboxykinase by biotin in diabetic rats. Mol Cell Biochem 132, 127–132 (1994). https://doi.org/10.1007/BF00926921

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Key Words

  • phosphoenolpyruvate carboxykinase
  • diabetes
  • transcriptional regulation
  • biotin