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Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor.

Authors :
NUCHE-BERENGUER, BERNARDO
PORTAL-NÚÑEZ, SERGIO
MORENO, PAOLA
GONZÁLEZ, NIEVES
ACITORES, ALICIA
LÓPEZ-HERRADÓN, ANA
ESBRIT, PEDRO
VALVERDE, ISABEL
VILLANUEVA-PEÑACARRILLO, MARÍA
Source :
Journal of Cellular Physiology. Nov2010, Vol. 225 Issue 2, p585-592. 8p. 1 Chart, 4 Graphs.
Publication Year :
2010

Abstract

Glucagon-like peptide 1 (GLP-1) controls glucose metabolism in extrapancreatic tissues through receptors other than the pancreatic cAMP-linked GLP-1 receptor; also, GLP-1 induces an insulin- and PTH-independent bone anabolic action in insulin-resistant and type-2 diabetic rats. Here we searched for the presence and characteristics of GLP-1 receptors in osteoblastic MC3T3-E1 cells. [125I]-GLP-1 specific binding to MC3T3-E1 cells was time- and temperature-dependent, reaching maximal value at 30 min at 25°C; in these conditions, [125I]-GLP-1 binding was dissociable, and displaced by GLP-1, partially by GLP-2, but not by exendin-4 (Ex-4), exendin-9 (Ex-9), glucagon or insulin; Scatchard analysis of the unlabeled GLP-1 data showed high and low affinity binding sites; cross-linking of GLP-1 binding revealed an estimated 70 kDa band, almost undetectable in the presence of 10-6 M GLP-1. GLP-1, Ex-9, insulin or glucagon failed to modify cellular cAMP content, while GLP-2 and Ex-4 increased it. However, GLP-1 induced an immediate hydrolysis of glycosylphosphatidylinositols (GPIs) generating short-lived inositolphosphoglycans (IPGs), and an increase in phosphatidylinositol-3 kinase (PI3K) and mitogen activated protein kinase (MAPK) activities; Ex-4 also affected GPIs, but its action was delayed with respect to that of GLP-1. This incretin was found to decrease Runx2 but increased osteocalcin gene expression, without affecting that of osteoprotegerin or the canonical Wnt pathway activity in MC3T3-E1 cells which do not express the pancreatic GLP-1 receptor. Our data demonstrate for the first time that GLP-1 can directly and functionally interact with osteoblastic cells, possibly through a GPI/IPG-coupled receptor. J. Cell. Physiol. 225: 585–592, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219541
Volume :
225
Issue :
2
Database :
Academic Search Index
Journal :
Journal of Cellular Physiology
Publication Type :
Academic Journal
Accession number :
53286191
Full Text :
https://doi.org/10.1002/jcp.22243