Hyperinsulinemia adversely affects lung structure and function
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Hyperinsulinemia adversely affects lung structure and function. / 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 A.
I: American Journal of Physiology - Lung Cellular and Molecular Physiology, Bind 310, Nr. 9, 01.05.2016, s. L837-45.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 179285004