Hyperinsulinemia adversely affects lung structure and function

Suchita Singh, Manish Bodas, Naveen K. Bhatraju, Bijay Pattnaik, Atish Gheware, Praveen Kolumam Parameswaran, Michael Thompson, Michelle Freeman, Ulaganathan Mabalirajan, Reinoud Gosens, Balaram Ghosh, Christina M Pabelick, Allan Linneberg, Y.s. Prakash, Anurag Agrawal

Research output: Contribution to journalArticle

22 Scopus citations

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 +g/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.

Original languageEnglish (US)
Pages (from-to)L837-L845
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number9
DOIs
StatePublished - Mar 1 2016

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Keywords

  • Hyperinsulinemia
  • Insulin resistance
  • Lung function
  • β-catenin

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology (medical)

Cite this

Singh, S., Bodas, M., Bhatraju, N. K., Pattnaik, B., Gheware, A., Parameswaran, P. K., Thompson, M., Freeman, M., Mabalirajan, U., Gosens, R., Ghosh, B., Pabelick, C. M., Linneberg, A., Prakash, Y. S., & Agrawal, A. (2016). Hyperinsulinemia adversely affects lung structure and function. American Journal of Physiology - Lung Cellular and Molecular Physiology, 310(9), L837-L845. https://doi.org/10.1152/ajplung.00091.2015