Glucagon-Like Peptide 1 And Atrial Natriuretic Peptide In A Female Mouse Model Of Obstructive Pulmonary Disease

Glucagon-like peptide-1 (GLP-1) is protective in lung disease models but the underlying mechanisms remain elusive. Because the hormone atrial natriuretic peptide (ANP) also has beneficial effects in lung disease, we hypothesized that GLP-1 effects may be mediated by ANP expression. To study this putative link, we used a mouse model of chronic obstructive pulmonary disease (COPD) and assessed lung function by unrestrained whole-body plethysmography. In 1 study, we investigated the role of endogenous GLP-1 by genetic GLP-1 receptor (GLP-1R) knockout (KO) and pharmaceutical blockade of the GLP-1R with the antagonist exendin-9 to -39 (EX-9). In another study the effects of exogenous GLP-1 were assessed. Lastly, we investigated the bronchodilatory properties of ANP and a GLP-1R agonist on isolated bronchial sections from healthy and COPD mice.Lung function did not differ between mice receiving phosphate-buffered saline (PBS) and EX-9 or between G LP-1R KO mice and their wild-type littermates. The COPD mice receiving G LP-1R agonist improved pulmonary function (P < .01) with less inflammation, but no less emphysema compared to PBS-treated mice. Compared with the PBS-treated mice, treatment with GLP-1 agonist increased ANP (nppa) gene expression by 10-fold (P < .01) and decreased endothelin-1 (P < .01), a peptide associated with bronchoconstriction. ANP had moderate bronchodilatory effects in isolated bronchial sections and GLP-1R agonist also showed bronchodilatory properties but less than ANP. Responses to both peptides were significantly increased in COPD mice (P < .05, P < .01).Taken together, our study suggests a link between GLP-1 and ANP in COPD. (C) Endocrine Society 2019.