Prevention of type I diabetes in nonobese diabetic mice by late intervention with nonhypercalcemic analogs of 1,25-dihydroxyvitamin D3 in combination with a short induction course of cyclosporin A

Endocrinology
K CasteelsRoger Bouillon

Abstract

In nonobese diabetic (NOD) mice, type I diabetes can be prevented without generalized immunosuppression by nonhypercalcemic analogs of vitamin D3 when treatment is started early, i.e. before the autoimmune attack, reflected by insulitis, occurs. The aim of this study was to investigate whether these substances can arrest progression to clinically overt diabetes when administered in a more advanced disease stage, namely when the autoimmune attack is ongoing, reflecting the situation in prediabetic subjects in whom immune intervention is being considered. We, therefore, evaluated the protective potential of MC1288 (20-epi-1,25-dihydroxyvitamin D3) a nonhypercalcemic analog of 1,25-dihydroxyvitamin D3, both alone and in combination with a short induction course of cyclosporin A, in NOD mice that already have insulitis, as demonstrated in pancreatic biopsies performed 15 days before the start oftherapy. Subsequently, mice were randomized into a control group, receiving the treatment vehicle (n = 26), and three treatment groups, receiving, respectively, 7.5 mg/kg x day cyclosporin A (CyA) from days 85-105 (n = 19), 0.1 microg/kg x 2 days MC1288 from days 85-200 (n = 20), or the combination of these two regimens (n = 20). At the time...Continue Reading

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