title: The H1-receptor antagonist cetirizine ameliorates high-fat diet-induced glucose intolerance in male C57BL/6 mice, but not diabetes outcome in female non-obese diabetic (NOD) mice.
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.
  
  
  CONCLUSIONS
  Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction.
authors.affiliation: Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University , Box 571, SE-751 23 Uppsala , Sweden.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Anvari
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Stellan
authors.initials: S
authors.lastname: Sandler
authors.forename: Nils
authors.initials: N
authors.lastname: Welsh
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001786:Blood Glucose / Q000378:metabolism; D017332:Cetirizine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D059305:Diet, High-Fat; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006967:Hypersensitivity; D007113:Immunity, Innate; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011969:Receptors, Histamine H1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D017332:Cetirizine
keywords: Beta-cell function; H1-receptor antagonists; NOD mice; glucose intolerance; high-fat diet