Pulmonary GLP-1 receptor increases at birth and exogenous GLP-1 receptor agonists augmented surfactant-protein levels in litters from normal and nitrofen-treated pregnant rats.
The glucagon-like peptide-1 receptor (GLP-1R) is found in a variety of tissues outside of the pancreas. For example, GLP-1R is expressed in the lung, where it has been implicated in the regulation of the lipid fraction of surfactants, suggesting it fulfills an important role in lung function. Here, we show that GLP-1R expression is strongly up-regulated immediately after birth in neonatal rats, particular in male offspring. Moreover, administering long half-life GLP-1R agonists to the mother from gestational day 14 to birth (exendin-4 or liraglutide) increased surfactant protein (SP)-A and SP-B mRNA expression and the amount of SPs in the amniotic fluid at the end of pregnancy. These effects were similar or more potent to those induced by the glucocorticoid dexamethasone, which also increased GLP-1R expression in fetuses just before delivery. Lir increased fetal SP-A and GLP-1R expression in control rats and in a nitrofen-induced model of lung hypoplasia. Moreover, lung size increased in controls after Lir administration, which also prevented the decrease in lung weight and the poor neonatal survival of the offspring from nitrofen-treated dams, effects that were not produced by dexamethasone. Taken together, our results demonstrate the importance of the GLP-1 system in regulating SP production and lung development.
Endocrinology Laboratory, Biomedical Research Centre (Centro Investigaciones Biomédicas), University of Vigo, Campus As Lagoas-Marcosende, E-36310 Vigo, Spain.
Marina
M
Romaní-Pérez
Verónica
V
Outeiriño-Iglesias
Manuel
M
Gil-Lozano
Lucas C
LC
González-Matías
Federico
F
Mallo
Eva
E
Vigo
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology; D000077270:Exenatide; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D000069450:Liraglutide; D008168:Lung / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010455:Peptides / Q000494:pharmacology; D010647:Phenyl Ethers / Q000633:toxicity; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D010647:Phenyl Ethers; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D014688:Venoms; D003907:Dexamethasone; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C007350:nitrofen