title: Hyperinsulinemia adversely affects lung structure and function.
abstract: 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.
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Suchita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Manish
authors.initials: M
authors.lastname: Bodas
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Bhatraju
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Bijay
authors.initials: B
authors.lastname: Pattnaik
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Atish
authors.initials: A
authors.lastname: Gheware
authors.affiliation: Departments of Anesthesiology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Praveen Kolumam
authors.initials: PK
authors.lastname: Parameswaran
authors.affiliation: Departments of Anesthesiology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Departments of Anesthesiology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Michelle
authors.initials: M
authors.lastname: Freeman
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Ulaganathan
authors.initials: U
authors.lastname: Mabalirajan
authors.affiliation: Department of Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, Groningen, Netherlands.
authors.forename: Reinoud
authors.initials: R
authors.lastname: Gosens
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India;
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.affiliation: Departments of Anesthesiology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Pabelick
authors.affiliation: Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Departments of Anesthesiology and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
authors.affiliation: Center of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India; a.agrawal@igib.in.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D007328:Insulin; D051176:beta Catenin
keywords: hyperinsulinemia; insulin resistance; lung function; β-catenin