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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The physiological role of glucagon-like peptide-1 in the regulation of renal function

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Author(s):
Farah, Livia X. S. [1] ; Valentini, Vanessa [1] ; Pessoa, Thaissa D. [2] ; Malnic, Gerhard [2] ; McDonough, Alicia A. [3] ; Girardi, Adriana C. C. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Heart Inst InCor, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Phys & Biophys, Sao Paulo - Brazil
[3] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 - USA
Total Affiliations: 3
Document type: Journal article
Source: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 310, n. 2, p. F123-F127, JAN 15 2016.
Web of Science Citations: 31
Abstract

Glucagon like peptide-1 (GLP-1) is an incretin hormone constantly secreted from the intestine at low basal levels in the fasted state; plasma concentrations rise rapidly after nutrient ingestion. Upon release, GLP-1 exerts insulinotropic effects via a G protein-coupled receptor, stimulation of adenylyl cyclase, and cAMP generation. Although primarily involved in glucose homeostasis, GLP-1 can induce diuresis and natriuresis when administered in pharmacological doses in humans and rodents. However, whether endogenous GLP-1 plays a role in regulating renal function remains an open question. This study aimed to test the hypothesis that blockade of GLP-1 receptor (GLP-1R) signaling at baseline influences renal salt and water handling. To this end, the GLP-1R antagonist exendin-9 (100 mu g.kg(-1).min(-1)) or vehicle was administered intravenously to overnight-fasted male Wistar rats for 30 min. This treatment reduced urinary cAMP excretion and renal cortical PKA activity, demonstrating blockade of renal GLP-1R signaling. Exendin-9- infused-rats exhibited reduced glomerular filtration rate, lithium clearance, urinary volume flow, and sodium excretion compared with vehicle-infused controls. Exendin-9 infusion also reduced renal cortical Na+/H+ exchanger isotope 3 (NHE3) phosphorylation at serine 552 (NHE3pS552), a PKA consensus site that correlates with reduced transport activity. Collectively, these results provide novel evidence that GLP-1 is a physiologically relevant natriuretic factor that contributes to sodium balance, in part via tonic modulation of NHE3 activity in the proximal tubule. (AU)

FAPESP's process: 13/10619-8 - Dipeptidyl peptidase IV as a potential target for the therapy of heart failure
Grantee:Adriana Castello Costa Girardi
Support type: Regular Research Grants
FAPESP's process: 12/10146-0 - Molecular mechanisms of regulation of the proximal tubular function in hypertension
Grantee:Adriana Castello Costa Girardi
Support type: Regular Research Grants