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

被引:122
作者
Schlatter, P.
Beglinger, C.
Drewe, J.
Gutmann, H.
机构
[1] Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland
[2] Univ Basel Hosp, Div Gastroenterol, CH-4031 Basel, Switzerland
关键词
porcine; proximal tubular cells; GLP-1; sodium;
D O I
10.1016/j.regpep.2006.12.016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu M). 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. (C) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:120 / 128
页数:9
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