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

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]

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

• 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 Opportunities: 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 Opportunities: Regular Research Grants