Since 2005, GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) have been developed as therapeutic agents for type 2 diabetes (T2D). GLP-1R is not only expressed in pancreatic islets but also other organs, especially the lung. However, controversy on extra-pancreatic GLP-1R expression still needs to be further resolved, utilizing different tools including the use of more reliable GLP-1R antibodies in immune-staining and co-immune-staining. Extra-pancreatic expression of GLP-1R has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs, aiming to repurpose them into therapeutic agents for other disorders. Extensive studies have demonstrated promising anti-inflammatory features of GLP-1RAs. Whether those features are directly mediated by GLP-1R expressed in immune cells also remains controversial. Following a brief review on GLP-1 as an incretin hormone and the development of GLP-1RAs as therapeutic agents for T2D, we have summarized our current understanding of the anti-inflammatory features of GLP-1RAs and commented on the controversy on extra-pancreatic GLP-1R expression. The main part of this review is a literature discussion on GLP-1RA utilization in animal models with chronic airway diseases and acute lung injuries, including studies on the combined use of mesenchymal stem cell (MSC) based therapy. This is followed by a brief summary.

There are more than two dozens of peptide hormones that are produced and released from the gastrointestinal (GI) tract. Among them, the incretin hormone glucagon-like peptide 1 (GLP-1) has received the most intensive attention for the past 30 years. Functional studies on GLP-1 and anoth?er gut incretin hormone glucose-dependent insulinotropic peptide (GIP) have led to the development of novel diabetes therapeutic agents known as GLP-1 receptor agonists and DPP-Ⅵinhibitors. Instead of forming endocrine glands, the gut hormone producing endocrine cells are widely spread throughout the entire GI tract, permitting vital interactions with the″external″environment. Here a brief introduction on GLP-1 and how nutritional components regulate its secretion were made, followed by reviewing some key development on how gut environment affects the production and secretion of GLP-1, including the contribution of gut microbiota.