Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells

Regul Pept. 2007 Jun 7;141(1-3):120-8. doi: 10.1016/j.regpep.2006.12.016. Epub 2007 Jan 10.


Background: GLP-1 is secreted into the circulation after food intake. The main biological effects of GLP-1 include stimulation of glucose dependent insulin secretion and induction of satiety feelings. Recently, it was demonstrated in rats and humans that GLP-1 can stimulate renal excretion of sodium. Based on these data, the existence of a renal GLP-1 receptor (GLP-1R) was postulated. However, the exact localization of the GLP-1R and the mechanism of this GLP-1 action have not yet been investigated.

Methods: Primary porcine proximal tubular cells were isolated from porcine kidneys. Expression of GLP-1R was measured at the mRNA level by quantitative RT-PCR. Protein expression of GLP-1R was verified with immunocytochemistry, immunohistochemistry and Western blot analysis. Functional studies included transport assessments of sodium and glucose using three different GLP-1 concentrations (200 pM, 2 nM and 20 nM), 200 pM exendin-4 (GLP-1 analogue) and an inhibitor of the dipeptidylpeptidase IV (DPPIV) enzyme (P32/98 at 10 microM). Finally, the expression of NHE3, the predominant Na(+)/H(+) exchanger in proximal tubular cells, was also investigated.

Results: GLP-1R, NHE3 and DPPIV were expressed at the mRNA level in porcine proximal tubular kidney cells. GLP-1R expression was confirmed at the protein level. Staining of human and pig kidney cortex revealed that GLP-1R was predominantly expressed in proximal tubular cells. Functional assays demonstrated an inhibition of sodium re-absorption with GLP-1 after 3 h of incubation. Exendin-4 and GLP-1 in combination with P32/98 co-administration had no clear influence on glucose and sodium uptake and transport.

Conclusion: GLP-1R is functionally expressed in porcine proximal tubular kidney cells. Addition of GLP-1 to these cells resulted in a reduced sodium re-absorption. GLP-1 had no effect on glucose re-absorption. We conclude that GLP-1 modulates sodium homeostasis in the kidney most likely through a direct action via its GLP-1R in proximal tubular cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Culture Techniques
  • Cells, Cultured
  • Dipeptidyl-Peptidase IV Inhibitors
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Exenatide
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide-1 Receptor
  • Glucose / analysis
  • Glucose / metabolism
  • Immunohistochemistry
  • Kidney Tubules, Proximal / cytology*
  • Kidney Tubules, Proximal / metabolism*
  • Kinetics
  • Pentanoic Acids / pharmacology
  • Peptides / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Glucagon / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium / antagonists & inhibitors
  • Sodium / metabolism
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / metabolism
  • Swine
  • Thiazolidines / pharmacology
  • Venoms / pharmacology


  • Dipeptidyl-Peptidase IV Inhibitors
  • Enzyme Inhibitors
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • P32-98 compound
  • Pentanoic Acids
  • Peptides
  • RNA, Messenger
  • Receptors, Glucagon
  • SLC9A3 protein, human
  • Slc9a3 protein, rat
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Thiazolidines
  • Venoms
  • Glucagon-Like Peptide 1
  • Sodium
  • Exenatide
  • Glucose