[Study of the role of insulin and insulin receptor in allergic airway inflammation of rats].

OBJECTIVE

To reveal the possible mechanism underlying the inverse relationship between IDDM and asthma and the role of insulin and insulin receptor in allergic airway inflammation.

METHODS

Diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin. Rats were sensitized by subcutaneous injection of ovalbumin (OVA) and challenged with an aerosolized solution of 1% OVA for 20 min 14 days after sensitization to provoke allergic airway inflammation. Sixty-four male Sprague-Dawley rats were divided into 8 groups: group A (asthma), group D (diabetes), group I (insulin treated), group AD (asthma + diabetes), group AI (asthma + insulin treated), group DI (diabetes + insulin treated), group ADI (asthma + diabetes + insulin treated), and group C (control). Blood glucose measurements, total and differential leukocyte counts and serum insulin measurements were carried out. Bronchoalveolar lavage (BAL) were performed, total and differential cell counts were determined. Hematoxylin-eosin stained paraffin section of lung tissue was examined to observe the histological changes. Immunohistochemistry method was used to describe the distribution of insulin receptor, and the expression of insulin receptor mRNA were measured by RT-PCR.

RESULTS

All groups of diabetes had higher blood glucose levels than non-diabetes groups. After antigen challenge, the rats of group A, AI, ADI exhibited airway inflammation characterized by significantly elevated eosinophils and neutrophils, group AD only exhibited mild airway inflammation. The serum insulin levels were higher in groups ADI, AI and A (27 mIU/L +/- 8 mIU/L, 83 mIU/L +/- 12 mIU/L, 71 mIU/L +/- 12 mIU/L respectively) compared with their respective control group (group DI, I, C, 15 mIU/L +/- 4 mIU/L, 64 mIU/L +/- 9 mIU/L; 49 mIU/L +/- 14 mIU/L respectively). Immunohistochemistry staining for insulin receptor revealed a diffused distribution pattern of the receptor in the lung tissue. Positive cells infiltrating in the alveolar spaces, submucosa of bronchus, blood vessels, and bronchial mucosa were increased significantly in groups A, AI and ADI. In groups with induced diabetes the expression of insulin receptor mRNA was elevated compared with that in the non-diabetes groups (0.2588 +/- 0.0809 vs 0.0896 +/- 0.0308, P = 0.00).

CONCLUSION

Administration of low dose insulin aggravated airway inflammation to antigen provocation in rats. Insulin secretion is increased in the presence of inflammation. In the lung of antigen-challenged rats, insulin receptors on the surface of the infiltrating inflammatory cells and bronchial secretory cells are increased.