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Glucagon-like peptide-1 functionally mediates the interaction between NHE3 and dipeptidyl peptidase IV in the renal proximal tubule (2013)

  • Authors:
  • Autor USP: MALNIC, GERHARD - ICB
  • Unidade: ICB
  • Subjects: FISIOLOGIA; RATOS WISTAR; TUBULOS RENAIS; PEPTIDEOS; GLUCAGON
  • Language: Português
  • Abstract: Introdução The activity of Na+/H+ exchanger isoform 3 (NHE3) is modified by a series of molecular mechanisms, among which association with other proteins. It has been previously shown that dipeptidyl peptidase IV (DPPIV) physically associates with NHE3 in the apical membrane of the renal proximal tubule (PT). Moreover, studies in vitro and in vivo have revealed that inhibition of the catalytic activity of DPPIV inhibits NHE3 activity. Glucagon-like peptide (GLP-1) is a substrate of DPPIV and exerts natriuretic effects in humans and in experimental animals. Based on these data, we postulated that GLP-1 may be a potential candidate to mediate the functional interaction between NHE3 and DPPIV. Objetivos This study aimed to test the hypothesis that GLP-1 mediates the interaction between NHE3 and DPPIV in the renal proximal tubule. Métodos Renal function was evaluated in male Wistar rats (Protocol # 1027/07) in response to acute intravenous administration of the DPPIV inhibitor sitagliptin (100 mg/kg) in the presence or absence of the antagonist of the GLP-1 receptor (GLP-1R) exendin-9 (100 µg/kg) or in the presence of the agonist of this receptor exendin-4 (µg/kg). The effect of these compounds on NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT.Resultados We have observed that the diuretic and natriuretic effects of the DPPIV inhibitor were blocked by exendin-9. Conversely, there was no additive effect on urinary flow and urinary sodium excretion when sitagliptin was infused with exendin-4, suggesting that the mechanism by which DPPIV inhibition promotes diuresis and natriuresis is dependent on GLP-1R activation. Moreover, increases in urinary flow and urinary sodium excretion induced by exendin-4 or sitagliptin was accompanied by increased bicarbonaturia, whereas the concomitant administration of sitagliptin and exendin-9 decreased sodium, bicarbonate and water excretion. By the means of stationary microperfusion we found that NHE3-mediated-PT bicarbonate reabsorption was reduced by exendin-4 (1.324 ± 0.168vs.2.001± 0.082nmol/cm2×s, P < 0.001) while it was slightly but not significantly increased by exendin-9 (2.183 ± 0.074 vs.2.001± 0.082nmol/cm2×s). Conclusão Together, our previous findings combined with the results presented in this study allow us to validate the hypothesis that inhibition of the catalytic activity of DPPIV increases the bioavailability of GLP-1, and therefore reduces the activity of NHE3. In summary, we conclude that GLP-1 mediates the functional interaction between DPPIV and NHE3 in the PT
  • Imprenta:
  • Source:
  • Conference titles: Reunião Anual da Federação de Sociedades de Biologia Experimental (FeSBE)
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    • ABNT

      FARAH, L. S. et al. Glucagon-like peptide-1 functionally mediates the interaction between NHE3 and dipeptidyl peptidase IV in the renal proximal tubule. 2013, Anais.. Caxambu: FeSBE, 2013. . Acesso em: 03 maio 2024.

    • APA

      Farah, L. S., Valentini, V., Pessoa, T. D., Girardi, A. C. C., & Malnic, G. (2013). Glucagon-like peptide-1 functionally mediates the interaction between NHE3 and dipeptidyl peptidase IV in the renal proximal tubule. In Resumos. Caxambu: FeSBE.

    • NLM

      Farah LS, Valentini V, Pessoa TD, Girardi ACC, Malnic G. Glucagon-like peptide-1 functionally mediates the interaction between NHE3 and dipeptidyl peptidase IV in the renal proximal tubule. Resumos. 2013 ;[citado 2024 maio 03 ]

    • Vancouver

      Farah LS, Valentini V, Pessoa TD, Girardi ACC, Malnic G. Glucagon-like peptide-1 functionally mediates the interaction between NHE3 and dipeptidyl peptidase IV in the renal proximal tubule. Resumos. 2013 ;[citado 2024 maio 03 ]

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