Hyperinsulinemia adversely affects lung structure and function

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 310; no. 9; p. L837
• Main Authors: Singh, Suchita, Bodas, Manish, Bhatraju, Naveen K, Pattnaik, Bijay, Gheware, Atish, Parameswaran, Praveen Kolumam, Thompson, Michael, Freeman, Michelle, Mabalirajan, Ulaganathan, Gosens, Reinoud, Ghosh, Balaram, Pabelick, Christina, Linneberg, Allan, Prakash, Y S, Agrawal, Anurag
• Format: Journal Article
• Language: English
• Published: United States 01-05-2016
• Subjects: Active Transport, Cell Nucleus; Animals; beta Catenin - metabolism; Cell Line; Humans; Hyperinsulinism - blood; Hyperinsulinism - pathology; Insulin - blood; Insulin Resistance; Lung - pathology; Lung - physiopathology; Male; Mice, Inbred BALB C; Myocytes, Smooth Muscle - physiology; Signal Transduction; β-catenin; lung function; hyperinsulinemia; insulin resistance
• ISSN: 1522-1504
• DOI: 10.1152/ajplung.00091.2015

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.