Pathogenesis of low dose streptozotocin induced diabetes in mice: requirement for ?1-adrenoceptor activation and vasoactive amine release

Abstract

Pancreatic islet inflammation and subsequent diabetes was induced by multiple low doses of streptozotocin in male C57 Bl/6J mice. The development of hyperglycaemia was almost completely prevented by treating the animals with the alpha 1-adrenoceptor antagonist prazosin (20 mg.kg-1.day-1) as well as by the vasoactive amine antagonists methysergide (50 mg.kg-1.day-1), disodium cromoglycate (100 mg.kg-1.day-1), pizotifen (5 mg.kg-1.day-1) or cyproheptadine (20 mg.kg-1.day-1). Treatment with vasoactive amine antagonists largely inhibited infiltration of pancreatic islets by L3T4+-lymphocytes and to a lesser extent by Lyt2+-cells. The infiltration of macrophages was not affected except after pizotifen treatment. These results indicate that alpha 1-adrenoceptor activation is required for disease development and that vasoactive amine release is a prerequisite for lymphocytic insulitis but not for macrophage infiltration of islets.