Pathogenesis of low dose streptozotocin induced diabetes in mice: requirement for alpha 1-adrenoceptor activation and vasoactive amine release.
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.
Martin
S
S
Diabetes Research Institute, University of Düsseldorf, FRG.
Kolb-Bachofen
V
V
Kiesel
U
U
Kolb
H
H
D000818:Animals; D004205:Cromolyn Sodium / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000517:prevention & control; D006633:Histamine Antagonists / Q000494:pharmacology*; D008784:Methysergide / Q000494:pharmacology*; D010918:Pizotyline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D006633:Histamine Antagonists; D011942:Receptors, Adrenergic, alpha; D010918:Pizotyline; D003533:Cyproheptadine; D004205:Cromolyn Sodium; D011224:Prazosin; D008784:Methysergide