Role of insulin in antigen-induced airway eosinophilia and neuronal M2 muscarinic receptor dysfunction

• Published in: Journal of applied physiology (1985) Vol. 85; no. 5; pp. 1708 - 1718
• Main Authors: Belmonte, K. E, Fryer, A. D, Costello, R. W
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.11.1998; American Physiological Society
• Subjects: Anatomy & physiology; Animals; Antigens - immunology; Asthma; Biological and medical sciences; Blood Glucose - metabolism; Blood Glucose - physiology; Bronchial Hyperreactivity - physiopathology; Bronchoconstriction - drug effects; Bronchoconstriction - physiology; Chronic obstructive pulmonary disease, asthma; Diabetes; Diabetes Mellitus, Experimental - physiopathology; Heart Rate - physiology; Heparin - pharmacology; Insulin; Insulin - physiology; Male; Medical sciences; Muscarinic Agonists - pharmacology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Neurons - drug effects; Neurons - physiology; Pneumology; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; Pulmonary Eosinophilia - pathology; Pulmonary Eosinophilia - physiopathology; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Vagus Nerve - physiology; Endocrinopathy; Animal model; Pancreatic hormone; Hyperreactivity; Pathophysiology; Rat; Respiratory disease; Diabetes mellitus; Rodentia; Inflammation; Respiratory system; Insulin; Eosinophil; Asthma; Recruitment; Antigen; Respiratory tract; Cholinergic receptor; Vertebrata; Mammalia; M2 Muscarinic receptor; Obstructive pulmonary disease
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1998.85.5.1708

1  Department of Environmental Health Sciences, School of Hygiene and Public Health, and 2  Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, The Johns Hopkins University, Baltimore, Maryland 21205 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. airway hyperreactivity; airway inflammation; diabetes; asthma; vagus nerves