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*Diabetes Type 1
Endocrinology Vol. 139, No. 5 2369-2374
Copyright © 1998 by The Endocrine Society

ARTICLES

Amelioration of Diabetes in Nonobese Diabetic Mice with Advanced Disease by Linomide-Induced Immunoregulation Combined with Reg Protein Treatment1

David J. Gross, Lola Weiss, Israel Reibstein, Joop van den Brand, Hiroshi Okamoto, Anne Clark and Shimon Slavin

Departments of Endocrinology and Metabolism (D.J.G.,), Bone Marrow Transplantation and Cancer Immunobiology Laboratory (L.W., I.R., S.S.), Hebrew University-Hadassah Medical Center, Jerusalem 91120, Israel; the Oxford Diabetes Research Laboratories, Radcliffe Infirmary (J.v.d.B., A.C.), Oxford, United Kingdom OX2 6HE; and the Department of Biochemistry, Tohoku University School of Medicine (H.O.), Sendai 98–77, Japan

Address all correspondence and requests for reprints to: David J. Gross, M.D., Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem 91120, Israel. E-mail: gross{at}vms.huji.ac.il

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 regenerating rat islet library, has been previously shown to induce expansion of ß-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 treatment with Reg alone in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease (glucose intolerant), only treatment with the combination of both agents, but not that with each separately, resulted in amelioration of diabetes. Our study suggests that treatment aimed at abrogation of autoimmunity combined with expansion of ß-cell mass constitutes a potential therapeutic approach for treatment of insulin-dependent diabetes mellitus.




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