Human Physiology

, Volume 45, Issue 6, pp 685–692 | Cite as

Effect of the Glucagon-like Peptide-1 Mimetic on Ion- and Osmoregulating Renal Functions in Normoglycemia and Hyperglycemia

  • A. V. KutinaEmail author
  • E. V. Balbotkina
  • T. A. Karavashkina
  • E. I. Shakhmatova


Incretins are hormones with a wide range of biological activity. We studied the ratio of the glycemic effect of the glucagon-like peptide-1 mimetic and its effect on the renal excretion of sodium and water. It was found that both effects depend on the initial blood concentration of glucose. In normoglycemia, exenatide had no effect on blood sugar level, but it significantly increased urinary sodium excretion and reabsorption of solute-free water. In hyperglycemia the blood glucose concentration was normalized by exenatide, while the excretion of sodium by the kidneys and the reabsorption of solute-free water were increased to a small extent. This pattern was found both in patients with type 2 diabetes mellitus and in rats with hyperglycemia induced by intraperitoneal injection of glucose.


hyperglycemia glucagon-like peptide-1 sodium solute-free water kidney diabetes mellitus exenatide 



This study was carried out in the framework of the state contract of the Federal Agency for Scientific Organizations of Russia (state registration no. АААА-А18-118012290371-3) and supported in part by the Russian Foundation for Fundamental Research, project no. 17-04-01216.


Conflict of interests. The authors declare that they have no conflict of interest connected with the publication of this article.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the biomedical ethics principles formulated in the 1964 Helsinki Declaration and its later amendments and approved by the bioethics commission of the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences (St. Petersburg). Informed consent was obtained from all individual participants involved in the study after their being explained the potential risks and advantages, as well as the essence of the future study.


  1. 1.
    Shestakova, M.V. and Vikulova, O.K., Modern pharmacotherapy of type 2 diabetes using analogues of glucagon-like peptide-1 (GLP-1), Sakharnyi Diabet, 2007, no. 1, p. 9.Google Scholar
  2. 2.
    Holst, J.J., Deacon, C.F., Vilsboll, T., et al., Glucagon-like peptide-1, glucose homeostasis and diabetes, Trends Mol. Med., 2008, vol. 14, no. 4, p. 161.CrossRefGoogle Scholar
  3. 3.
    Galstyan, G.R., Karataeva, E.A., and Yudovich, E.A., Evolution of glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes, Sakharnyi Diabet, 2017, vol. 20, no. 4, p. 286.Google Scholar
  4. 4.
    Biryukova, E.V. and Yakubova, T.R., Byetta: past, present, and future, Eff. Farmakoter., 2015, no. 11, p. 34.Google Scholar
  5. 5.
    Gallwitz, B., Novel therapeutic approaches in diabetes, Endocrinol. Dev., 2016, vol. 31, p. 43.CrossRefGoogle Scholar
  6. 6.
    Nauck, M.A. and Meier, J.J., Incretin hormones: their role in health and disease, Diabetes Obes. Metab., 2018, vol. 20, suppl. 1, p. 5.CrossRefGoogle Scholar
  7. 7.
    Natochin, Yu.V., Marina, A.S., and Kutina, A.V., The role of incretin as an integrator of sodium and water balance regulation, Dokl. Biol. Sci., 2014, vol. 458, no. 1, p. 271.CrossRefGoogle Scholar
  8. 8.
    Crajoinas, R.O., Oricchio, F.T., Pessoa, T.D., et al., Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1, Am. J. Physiol. Renal Physiol., 2011, vol. 301, no. 2, p. F355.CrossRefGoogle Scholar
  9. 9.
    Kutina, A.V., Golosova, D.V., Marina, A.S., et al., Role of Vasopressin in the regulation of renal sodium excretion: interaction with glucagon-like peptide-1, J. Neuroendocrinol., 2016, vol. 28, no. 4.
  10. 10.
    Shutskaya, Zh.V., Shakhmatova, E.I., Kuznetsova, A.A., and Natochin, Yu.V., The role of the kidneys in the regulation of osmolality and concentrations of cations in the blood serum in hyperglycemia, Hum. Physiol., 2008, vol. 34, no. 5, p. 601.CrossRefGoogle Scholar
  11. 11.
    Shakhmatova, E.I., Pimenova, E.V., and Shutskaya, Zh.V., The influence of Byetta (Exenatide) on the osmoregulatory function of the kidneys in humans with diabetes mellitus, Eksp. Klin. Farmakol., 2014, vol. 77, no. 3, p. 24.PubMedGoogle Scholar
  12. 12.
    De Vogel-van den Bosch, J., Hoeks, J., Timmers, S., et al., The effects of long- or medium-chain fat diets on glucose tolerance and myocellular content of lipid intermediates in rats, Obesity, 2011, vol. 19, no. 4, p. 792.CrossRefGoogle Scholar
  13. 13.
    Tonneijck, L., Smits, M.M., Muskiet, M.H., et al., Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomized, double-blind, placebo-controlled trial, Diabetologia, 2016, vol. 59, no. 7, p. 1412.CrossRefGoogle Scholar
  14. 14.
    Tonneijck, L., Smits, M.M., Muskiet, M.H., et al., Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial, Diabetes Care, 2016, vol. 39, no. 11, p. 2042.CrossRefGoogle Scholar
  15. 15.
    von Scholten, B.J., Hansen, T.W., Goetze, J.P., et al., Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes, J. Diabetes Complications, 2015, vol. 29, no. 5, p. 670.CrossRefGoogle Scholar
  16. 16.
    Skov, J., Pedersen, M., Holst, J.J., et al., Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial, Diabetes Obes. Metab., 2016, vol. 18, no. 6, p. 581.CrossRefGoogle Scholar
  17. 17.
    Muskiet, M.H., Tonneijck, L., Smits, M.M., et al., Acute renal haemodynamic effects of glucagon-like peptide-1 receptor agonist exenatide in healthy overweight men, Diabetes Obes. Metab., 2016, vol. 18, no. 2, p. 178.CrossRefGoogle Scholar
  18. 18.
    Schlatter, P., Beglinger, C., Drewe, J., and Gutmann, H., Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells, Regul. Pept., 2007, vol. 141, no. 1–3, p. 120.CrossRefGoogle Scholar
  19. 19.
    Thomson, S.C., Kashkouli, A., and Singh, P., Glucagon-like peptide-1 receptor stimulation increases GFR and suppresses proximal reabsorption in the rat, Am. J. Physiol. Renal Physiol., 2013, vol. 304, no. 2, p. F137.CrossRefGoogle Scholar
  20. 20.
    Roscoe, J.M., Halperin, M.L., Rolleston, F.S., and Goldstein, M.B., Hyperglycemia-induced hyponatremia: metabolic considerations in calculation of serum sodium depression, Can. Med. Assoc. J., 1975, vol. 112, no. 4, p. 452.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Mozaffari, M.S. and Schaffer, S.W., Impaired saline-stimulated diuresis and natriuresis in the conscious hypertensive glucose-intolerant rat, Am. J. Hypertens., 2002, vol. 15, no. 1, p. 58.CrossRefGoogle Scholar
  22. 22.
    Marwaha, A. and Lokhandwala, M.F., Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in obese Zucker rats, Clin. Exp. Hypertens., 2003, vol. 25, no. 8, p. 509.CrossRefGoogle Scholar
  23. 23.
    Arumugam, S., Sreedhar, R., Miyashita, S., et al., Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy, Exp. Mol. Pathol., 2014, vol. 97, no. 1, p. 137.CrossRefGoogle Scholar
  24. 24.
    Brands, M.W. and Manhiani, M.M., Sodium-retaining effect of insulin in diabetes, Am. J. Physiol.-Regul. Integr. Comp. Physiol., 2012, vol. 303, no. 11, p. R1101.CrossRefGoogle Scholar
  25. 25.
    Ueda-Nishimura, T., Niisato, N., Miyazaki, H., et al., Synergic action of insulin and genistein on Na+/K+/2Cl cotransporter in renal epithelium, Biochem. Biophys. Res. Commun., 2005, vol. 332, no. 4, p. 1042.CrossRefGoogle Scholar
  26. 26.
    Chavez-Canales, M., Arroyo, J.P., Ko, B., et al., Insulin increases the functional activity of the renal NaCl cotransporter, J. Hypertens., 2013, vol. 31, no. 2, p. 303.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Blazer-Yost, B.L., Esterman, M.A., and Vlahos, C.J., Insulin-stimulated trafficking of ENaC in renal cells requires PI3-kinase activity, Am. J. Physiol., Cell. Physio-l., 2003, vol. 284, p. C1645.CrossRefGoogle Scholar
  28. 28.
    Irsik, D.L., Blazer-Yost, B.L., Staruschenko, A., and Brands, M.W., The normal increase in insulin after a meal may be required to prevent postprandial renal sodium and volume losses, Am. J. Physiol.-Regul. Integr. Comp. Physiol., 2017, vol. 312, no. 6, p. R965.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • A. V. Kutina
    • 1
    Email author
  • E. V. Balbotkina
    • 1
  • T. A. Karavashkina
    • 1
  • E. I. Shakhmatova
    • 1
  1. 1.Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesSt. PetersburgRussia

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