Hyperinsulinemia adversely affects lung structure and function

Abstract

A. Hyperinsulinemia adversely affects lung structure and function.

Author response to letter to editor: Hyperinsulinemia adversely affects lung structure and function

“…The primary objection raised by Wolff et al (17) seems to be to a statement in our article that "Our work has important general implications that should hopefully lead to questioning of many current trends or practices including use of inhaled insulin formulations in diabetes" and of the data behind the statement (11). After a careful review of the critique by Wolff et al (17), we stand by our statement.…”

“…We appreciate the interest shown by Wolff et al (17) regarding our recent publication in the American Journal of Physiology Lung Cellular and Molecular Physiology (11). We acknowledge the convenience of an inhaled insulin formulation, the extensive safety data required by the FDA prior to approval, and also the inherently unknown nature of long-term side effects of any drug despite appropriate safety studies and extensive financial investment by the parent company, academia and various organizations.…”

“…In terms of mechanisms, we have presented multiple lines of evidence using experiments on freshly dissected human lung tissue as well as mice, which lead us to conclude that high levels of insulin activate ␤-catenin signaling in the lung that further leads to remodeling (11). Regarding these, Wolff et al have raised concerns only about the mouse data and therefore they likely agree that insulin induces ␤-catenin signaling in human lung tissue and drives airway smooth muscle proliferation, contractility, and collagen deposition in vitro.…”

Metabolic consequences of obesity as an “outside in” mechanism of disease severity in asthma

“…[9] is topical because recent studies in cell culture and mouse models suggest that insulin can cause lung tissue remodelling and worsen lung function [10]. Specifically, it has been shown that insulin stimulates primary human airway smooth muscle cells to proliferate and release collagen [10]. In addition, intranasal insulin administration to mice causes peribronchial fibrosis and airway hyperresponsiveness [10].…”

“…Specifically, it has been shown that insulin stimulates primary human airway smooth muscle cells to proliferate and release collagen [10]. In addition, intranasal insulin administration to mice causes peribronchial fibrosis and airway hyperresponsiveness [10]. Thus, hyperinsulinaemia may act on insulin receptors on multiple lung cells to change airway structure and function.…”