Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C

Michael B Wheeler; Ming Lu; Joseph S Dillon; Xing-Hong Leng; Chuan Chen; Aubrey E Boyd

doi:10.1210/endo.133.1.8391428

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Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C

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Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C

Michael B Wheeler, Ming Lu, Joseph S Dillon, Xing-Hong Leng, Chuan Chen and Aubrey E Boyd

Endocrinology (Philadelphia), Vol.133(1), pp.57-62

07/1993

DOI: 10.1210/endo.133.1.8391428

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Abstract

In man, glucagon-like peptide-I-(7-37) [GLP-I-(7-37)] is the most potent endogenous insulin-stimulating hormone. Although GLP-I-(7-37)-stimulated insulin secretion from the beta-cell is associated with an increase in cAMP accumulation, little is known about the signal transduction pathways used by this peptide. Using a cDNA encoding a high affinity rat GLP-I-(7-37) receptor [Kd = 4.1 nM for GLP-I-(7-37); Kd = 1 microM for GLP-I-(1-36) amide] expressed in a monkey kidney cell line (COS-7), we have demonstrated that the receptor is not only coupled to adenylyl cyclase, but is associated with an increase in the free cytosolic calcium level ([Ca2+]i). GLP-I-(7-37) increased both cAMP and [Ca2+]i in a dose-dependent manner and with equal potency (ED50 = 2.0 nM). The major source of the increased [Ca2+]i was found to be through the release of intracellular pools of Ca2+ associated with an increase in phosphoinositol turnover. Northern blot hybridization studies demonstrated that the GLP-I-(7-37) receptor gene was expressed in relatively high abundance in pancreatic islets and lung, but was also expressed at lower levels in the brain, liver, kidney, and skeletal muscle. This study establishes that a single GLP-I receptor species can mediate the effects of GLP-I-(7-37) through multiple G-protein-coupled signaling pathways, including the adenylyl cyclase system, phospholipase-C, and changes in [Ca2+]i.

Details

Title: Subtitle: Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C
Creators: Michael B Wheeler - Tufts Medical Center
Ming Lu - Tufts Medical Center
Joseph S Dillon - Tufts Medical Center
Xing-Hong Leng - Tufts Medical Center
Chuan Chen - Tufts Medical Center
Aubrey E Boyd - Tufts Medical Center
Resource Type: Journal article
Publication Details: Endocrinology (Philadelphia), Vol.133(1), pp.57-62
DOI: 10.1210/endo.133.1.8391428
ISSN: 0013-7227
eISSN: 1945-7170
Language: English
Date published: 07/1993
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359927702771

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