TY - JOUR

T1 - Hyperinsulinemia adversely affects lung structure and function

AU - Singh, Suchita

AU - Bodas, Manish

AU - Bhatraju, Naveen K

AU - Pattnaik, Bijay

AU - Gheware, Atish

AU - Parameswaran, Praveen Kolumam

AU - Thompson, Michael

AU - Freeman, Michelle

AU - Mabalirajan, Ulaganathan

AU - Gosens, Reinoud

AU - Ghosh, Balaram

AU - Pabelick, Christina

AU - Linneberg, Allan

AU - Prakash, Y S

AU - Agrawal, Anurag A.

N1 - Copyright © 2016 the American Physiological Society.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Active Transport, Cell Nucleus

KW - Animals

KW - Cell Line

KW - Humans

KW - Hyperinsulinism

KW - Insulin

KW - Insulin Resistance

KW - Lung

KW - Male

KW - Mice, Inbred BALB C

KW - Myocytes, Smooth Muscle

KW - Signal Transduction

KW - beta Catenin

KW - Journal Article

U2 - 10.1152/ajplung.00091.2015

DO - 10.1152/ajplung.00091.2015

M3 - Journal article

C2 - 26919895

VL - 310

SP - L837-45

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 9

ER -