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Down-regulation of mast cell activation and airway reactivity in diabetic rats: role of insulin

¹ Research Division, Institute of Heart (INCOR), and ² Dept of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, and ³ Dept of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, Rio de Janeiro, Brazil

CORRESPONDENCE: P. Sannomiya, Research Division, Institute of Heart (INCOR), LIM-11, University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar 44, 05403-000 São Paulo, SP, Brazil. Fax: 55 1130667178. E-mail: exppaulina@incor.usp.br

Keywords: Allergy, asthma, diabetes mellitus, mast cells

Received: November 24, 2003
Accepted June 9, 2004

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo e Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Hormones play a modulating role in allergic inflammation. An inverse relationship between atopy and diabetes mellitus was reported. The mechanisms regulating this interaction are not completely understood. This study examined whether insulin influences mast cell activation following antigen challenge in rats.

The experimental design included alloxan-induced diabetic rats and matching controls. Experiments were performed 30 days after alloxan injection. The animals were sensitised by s.c. injection of ovalbumin (OA) and aluminium hydroxide. OA-induced airway contraction, morphometric analysis of airway mast cells and tissue histamine quantification were evaluated in the isolated main bronchus and intrapulmonary bronchus upon exposure to antigen in vitro.

Relative to controls, a reduced contraction to OA was observed in bronchial segments isolated from diabetic rats. This was accompanied by a 50% reduction in the number of degranulated mast cells and in histamine release. A complete recovery of the impaired responses was observed under the influence of insulin.

In conclusion, the data suggested that insulin might modulate the controlling of mast cell degranulation; therefore, the early-phase response to antigen provocation, which represents a new insight into a better understanding of the mechanisms, accounted for the decreased risk of asthma among type-1 diabetic patients.