Cell and Developmental Biology Commons^™

Increased Airway Reactivity And Hyperinsulinemia In Obese Mice Are Linked By Erk Signaling In Brain Stem Cholinergic Neurons, Luiz O. S. Leiria, Fernanda M. Arantes-Costa, Marina C. Calixto, Eduardo C. Alexandre, Rodrigo F. Moura, Franco Folli, Carla M. Prado, Marco Antonio Prado, Vania F. Prado, Licio A. Velloso, Jose Donato Jr., Edson Antunes, Milton A. Martins, Mario J. A. Saad

Anatomy and Cell Biology Publications

Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR). In obesity-associated asthma, AHR may be regulated by non-T(H)2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV)-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KDHOM-/-), mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK) normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located …