In addition, a high insulin concentration could inhibit muscarinic M2 receptors on pulmonary parasympathetic nerves in both humans and mice to increase airway hyperresponsiveness[12] and can also directly contribute to endothelial cell damage and the proliferation of airway smooth muscle cells, potentially resulting in airway narrowing.[44] According to the results of Park, YH et al, expression of TGF-β1 is upregulated in the bronchial epithelium due to IR, which may be essential for airway hyperresponsiveness and development of lung fibrosis. Here, INS is linked to airway hyperresponsiveness.