Pathogenesis of low dose streptozotocin induced diabetes in mice: requirement for α1-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 α1-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 (100mg·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 α1-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. © 1989 Springer-Verlag.