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

K. E. Belmonte, Allison Fryer, R. W. Costello

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

In the lungs, neuronal M2 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 M2 receptor function. Because there is a low incidence of asthma among diabetic patients, we investigated whether diabetes protects neuronal M2 receptor function in antigen-challenged rats. Antigen challenge of sensitized rats decreased M2 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 M2 receptor function was preserved and there was no eosinophil accumulation around airway nerves. Insulin treatment of diabetic rats completely restored loss of M2 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 M2 muscarinic receptor function, and subsequent hyperresponsiveness in antigen-challenged rats and may explain decreased incidence of asthma among diabetic humans.

Original languageEnglish (US)
Pages (from-to)1708-1718
Number of pages11
JournalJournal of Applied Physiology
Volume85
Issue number5
StatePublished - Nov 1998
Externally publishedYes

Fingerprint

Muscarinic M2 Receptors
Eosinophilia
Insulin
Antigens
Eosinophils
Asthma
Incidence
Inflammation
Lung

Keywords

  • Airway hyperreactivity
  • Airway inflammation
  • Asthma
  • Diabetes
  • Vagus nerves

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Role of insulin in antigen-induced airway eosinophilia and neuronal M2 muscarinic receptor dysfunction. / Belmonte, K. E.; Fryer, Allison; Costello, R. W.

In: Journal of Applied Physiology, Vol. 85, No. 5, 11.1998, p. 1708-1718.

Research output: Contribution to journalArticle

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