Amelioration of Diabetes in Nonobese Diabetic Mice with Advanced Disease by Linomide-Induced Immunoregulation Combined with Reg Protein Treatment

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Abstract
Oral linomide, (quinoline-3-carboxamide), has been shown to prevent autoimmune insulitis, islet destruction, and diabetes in NOD mice treated at an early stage of the disease, but confers only partial protection in animals with advanced disease. Reg protein, the gene product of a complementary DNA isolated from a regen- erating rat islet library, has been previously shown to induce ex- pansion of b-cell mass in pancreatectomized rats. To determine the effect of treatment combining immunomodulation and Reg protein on advanced autoimmune diabetes, we treated female NOD mice with oral linomide and ip Reg protein injections. In 14-week-old animals with less severe disease (glucose tolerant), treatment with each agent alone resulted in amelioration of diabetes, as did treat- ment with Reg alone in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease (glucose intolerant), only treat- ment with the combination of both agents, but not that with each separately, resulted in amelioration of diabetes. Our study sug- gests that treatment aimed at abrogation of autoimmunity com- bined with expansion of b-cell mass constitutes a potential ther- apeutic approach for treatment of insulin-dependent diabetes mellitus. (Endocrinology 139: 2369 -2374, 1998)

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