The Adenosine Receptor Agonist 5’-N-Ethylcarboxamide-Adenosine Increases Glucose 6-Phosphatase Expression and Gluconeogenesis


Intraperitoneal administration of the non-selective adenosine receptor agonist 5’-N-ethylcarboxamide-adenosine (NECA) (0.1 or 0.3 mg/kg) increased fasting serum glucose levels in mice. To clarify the mechanism responsible for this, the expression of liver glucose 6-phosphatase (G6Pase: a gluconeogenic enzyme) was analyzed, and it was found that G6Pase mRNA was increased by NECA treatment. Administration of 0.3 mg/kg NECA resulted in elevated serum glucose levels at 1 h and were further elevated at 6 h. Administration of 0.1 mg/kg NECA increased serum glucose levels at 1 h and had returned to control levels by 6 h. The increase in fasting serum glucose levels induced by NECA are thought to be caused, in part, by elevated G6Pase expression.

Share and Cite:

K. Matsuda, Y. Horikawa, Y. Sasaki and S. Sakata, "The Adenosine Receptor Agonist 5’-N-Ethylcarboxamide-Adenosine Increases Glucose 6-Phosphatase Expression and Gluconeogenesis," Pharmacology & Pharmacy, Vol. 5 No. 1, 2014, pp. 19-23. doi: 10.4236/pp.2014.51004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. A. Challis, L. Budohoski, B. McManus and E. A. Newsholme, “Effects of an Adenosine-Receptor Antagonist on Insulin-Resistance in Soleus Muscle from Obese Zucker Rats,” Biochemical Journal, Vol. 221, No. 3, 1984, pp. 915-917.
[2] B. B. Fredholm, E. Irenius, B. Kull and G. Schulte, “Comparison of the Potency of Adenosine as an Agonist at Human Adenosine Receptors Expressed in Chinese Hamster Ovary Cells,” Biochemical Pharmacology, Vol. 61, No. 4, 2001, pp. 443-448.
[3] H. Hagberg, P. Andersson, J. Lacarewicz, I. Jacobson, S. Butcher and M. Sandberg, “Extracellular Adenosine, Inosine, Hypoxanthine, and Xanthine in Relation to Tissue Nucleotides and Purines in Rat Striatum during Transient Ischemia,” Journal of Neurochemistry, Vol. 49, No. 1, 1987, pp. 227-231.
[4] B. B. Fredholm, A. P. Ijzerman, K. A. Jacobson, K.-N Klotz and J. Linden, “International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors,” Pharmacological Reviews, Vol. 53, No. 4, 2001, pp. 527-552.
[5] C. St. Hilaire, S. H. Carroll, H. Chen and K. Ravid, “Mechanisms of Induction of Adenosine Receptor Genes and Its Functional Significance,” Journal of Cellular Physiology, Vol. 218, No. 1, 2009, pp. 35-44.
[6] M. R. Blackburn, C. O. Vance, E. Morschl and C. N. Wilson, “Adenosine Receptors and Inflammation,” Handbook of Experimental Pharmacology, Vol. 193, 2009, pp. 215-269.
[7] R. A. Figler, G. Wang, S. Srinivasan, D. Y. Jung, Z. Zhang, J. S. Pankow, K. Ravid, B. Fredholm, C. C. Hedrick, S. S. Rich, J. K. Kim, K. F. LaNoue and J. Linden, “Links between Insulin Resistance, Adenosine A2B Receptors, and Inflammatory Markers in Mice and Humans,” Diabetes, Vol. 60, No. 2, 2011, pp. 669-679.
[8] H. Johnston-Cox, M. Koupenova, D. Yang, B. Corkey, N. Gokce, M. G. Farb, N. LeBrasseur and K. Ravid, “The A2b Adenosine Receptor Modulates Glucose Homeostasis and Obesity,” PLoS One, Vol. 7, No. 7, 2012, Article ID: e40584.
[9] N. Yasuda, T. Inoue, T. Horizoe, K. Nagata, H. Minami, T. Kawata, Y. Hoshino, H. Harada, S. Yoshikawa, O. Asano, J. Nagaoka, M. Murakami, S. Abe, S. Kobayashi and I. Tanaka, “Functional Characterization of the Adenosine Receptor Contributing to Glycogenolysis and Gluconeogenesis in Rat Hepatocytes,” European Journal of Pharmacology, Vol. 459, No. 2-3, 2003, pp. 159-166.
[10] C. A. Lalli, J. R. Pauli, P. O. Prada, D. E. Cintra, E. R. Ropelle, L. A. Velloso and M. J. Saad, “Statin Modulates Insulin Signaling and Insulin Resistance in Liver and Muscle of Rats Fed a High-fat Diet,” Metabolism, Vol. 57, No. 1, 2008, pp. 57-65.
[11] S. F. Sakata, M. Fujino, K. Matsuda, M. Maeda, H. Ohira, K. Kawasaki and N. Tamaki, “Mechanism of Liver Tyrosine Aminotransferase Increase in Ethanol-Treated Mice and Its Effect on Serum Tyrosine Level,” Journal of Nutritional Science and Vitaminology, Vol. 53, No. 6, 2007, pp. 489-495.
[12] M. Sharifzadeh, M. R. Zarrindast and M. Samini, “Effects of Adenosine Analogues on Apomorphine-Induced Penile Erection in Rats,” General Pharmacology, Vol. 26, No. 8, 1995, pp. 1785-1790.
[13] P. Chomczynski and N. Sacchi, “Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenolchloroform Extraction,” Analitical Biochemistry, Vol. 162, No. 1, 1987, pp. 156-159.
[14] S. F. Sakata, S. Okumura, K. Matsuda, Y. Horikawa, M. Maeda, K. Kawasaki, J. Y. Chou and N. Tamaki, “Effect of Fasting on Methionine Adenosyltransferase Expression and the Methionine Cycle in the Mouse Liver,” Journal of Nutritional Science and Vitaminology, Vol. 51, No. 2, 2005, pp. 118-123.
[15] M. Dubois, K. A. Gilles, J. K. Hamilton, P. A. Rebers and F. Smith, “Colorimetric Method for Determination of Sugars and Related Substances,” Analitical Chemistry, Vol. 28, No. 3, 1956, p. 350.
[16] H. G. Hers, “The Control of Glycogen Metabolism in the Liver,” Annual Review of Biochemistry, Vol. 45, 1976, pp. 167-189.
[17] J. S. Garrow, W. P. T. James and A. Ralph, “Human Nutrition and Dietetics,” Churchill Livingstone, Edinburgh, 2000, p. 82.
[18] R. C. Garland, “Induction of Glucose 6-Phosphatase in Cultured Hepatoma Cells by Dexamethasone,” Biochemical Biophysical Research Communications, Vol. 139, No. 3, 1986, pp. 1130-1134.
[19] W. M. van Weerden, H. G. Bierings, G. J. van Steenbrugge, F. H. de Jong and F. H. Schroder, “Adrenal Glands of Mouse and Rat Do Not Synthesize Androgens,” Life Science, Vol. 50, No. 12, 1992, pp. 857-861.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.