Role of insulin in antigen-induced airway eosinophilia and neuronal M 2 muscarinic receptor dysfunction

• Published in: Journal of applied physiology (1985) 1998-11, Vol.85 (5), p.1708-1718
• Main Authors: Belmonte, K. E., Fryer, A. D., Costello, R. W.
• Format: Article
• Language: English
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1998.85.5.1708

In the lungs, neuronal M 2 muscarinic receptors limit ACh release from parasympathetic nerves. In antigen-challenged animals, eosinophil proteins block these receptors, resulting in increased ACh release and vagally mediated hyperresponsiveness. In contrast, diabetic rats are hyporesponsive and have increased M 2 receptor function. Because there is a low incidence of asthma among diabetic patients, we investigated whether diabetes protects neuronal M 2 receptor function in antigen-challenged rats. Antigen challenge of sensitized rats decreased M 2 receptor function, increased vagally mediated hyperreactivity by 75%, and caused a 10-fold increase in eosinophil accumulation around airway nerves. In antigen-challenged diabetic rats, neuronal M 2 receptor function was preserved and there was no eosinophil accumulation around airway nerves. Insulin treatment of diabetic rats completely restored loss of M 2 receptor function, vagally mediated hyperresponsiveness, and eosinophilia after antigen challenge. These data demonstrate that insulin is required for development of airway inflammation, loss of neuronal M 2 muscarinic receptor function, and subsequent hyperresponsiveness in antigen-challenged rats and may explain decreased incidence of asthma among diabetic humans.