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2016 ; 310
(9
): L837-45
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Hyperinsulinemia adversely affects lung structure and function
#MMPMID26919895
Singh S
; Bodas M
; Bhatraju NK
; Pattnaik B
; Gheware A
; Parameswaran PK
; Thompson M
; Freeman M
; Mabalirajan U
; Gosens R
; Ghosh B
; Pabelick C
; Linneberg A
; Prakash YS
; Agrawal A
Am J Physiol Lung Cell Mol Physiol
2016[May]; 310
(9
): L837-45
PMID26919895
show ga
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 ?-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 ?-catenin in lung
tissue and the contractile effects on ASM cells may be causally related to the
development of asthma-like phenotype.