GLP-1 and pulmonary diseases

GLP-1 and pulmonary diseasesRecently we showed that GLP-1 could improve lung function and reduce mortality in a model of murine chronic obstructive pulmonary disease (COPD). GLP-1 is an incretin hormone acting as a secretagogue of insulin and analogues are therefore marketed to treat type 2 diabetes. The effect observed in the COPD model was very surprising. 

We hypothesize that the beneficial effects of GLP-1 on pulmonary function is obtained through a secretion of atrial natriuretic peptide (ANP) from either the atrial myocytes or from ANP secreting cells in lung tissue. ANP is a hormone important for the regulation of blood pressure, but has also shown to relax bronchial smooth muscle cells, thereby decreasing airway obstruction. ANP was recently shown to be secreted from atrial myocyte upon GLP-1 stimulation, thereby acting as a second messenger for the cardiovascular effects which has been observed after treatment with GLP-1 analogues. ANP in itself has got a very short half-life and cannot be used as a bronchodilator, but if GLP-1 analogues can be used to stimulate a rapid ANP secretion, GLP-1 analogues can have a therapeutic role in the treatment of acute airway obstruction in exacerbations of pulmonary diseases. This finding can have a major impact on the treatment strategy of e.g. acute exacerbations in COPD, a widespread disease with a high morbidity and mortality.

The project is funded by The Danish Research Council.