Abstract
Background. It has been proposed that the histamine 1-receptor (H1-receptor) not only promotes allergic reactions, but also modulates innate immunity and autoimmune reactions. In line with this, we have recently reported that the H1-receptor antagonist cetirizine partially counteracts cytokine-induced beta-cell signaling and destruction. Therefore, the aim of this study was to determine whether cetirizine affects diabetes in NOD mice, a model for human type 1 diabetes, and glucose intolerance in high-fat diet C57BL/6 mice, a model for human glucose intolerance.Methods. Female NOD mice were treated with cetirizine in the drinking water (25 mg/kg body weight) from 9 until 30 weeks of age during which precipitation of diabetes was followed. Male C57BL/6 mice were given a high-fat diet from 5 weeks of age. When the mice were 12 weeks of age cetirizine was given for 2 weeks in the drinking water. The effects of cetirizine were analyzed by blood glucose determinations, glucose tolerance tests, and insulin sensitivity tests.Results. Cetirizine did not affect diabetes development in NOD mice. On the other hand, cetirizine treatment for 1 week protected against high-fat diet-induced hyperglycemia. The glucose tolerance after 2 weeks of cetirizine treatment was improved in high-fat diet mice. We observed no effect of cetirizine on the insulin sensitivity of high-fat diet mice.Conclusion. Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction.
Highlights
Histamine 1 (H1)-receptor antagonists are commonly used in the treatment of allergic disorders, but histamine may influence non-allergic inflammatory and autoimmune events [1]
Cetirizine did not protect against development of diabetes in non-obese diabetes (NOD) mice The precipitation of overt diabetes in female NOD mice usually occurs from approximately 15 weeks of age
To study whether the activity of the H1-receptor affects the onset of disease, we treated female NOD mice from 9 to 30 weeks of age with 25 mg/kg body weight per day of cetirizine administered via the drinking water
Summary
Histamine 1 (H1)-receptor antagonists are commonly used in the treatment of allergic disorders, but histamine may influence non-allergic inflammatory and autoimmune events [1]. As type 1 diabetes is an autoimmune disease in which pancreatic beta-cells are destroyed via inflammatory and T-cell-mediated events [11], and as type 2 diabetes is associated with macrophage activation and increased release of pro-inflammatory cytokines [12], it is possible that histamine via activation of the H1-receptor modulates events pertinent to the pathogenesis of both type 1 and type 2 diabetes Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction
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