Successful islet transplantation in spontaneous diabetes.
Optimism for islet transplantation is based on reversal of diabetes artificially induced in animals by pancreatectomy or beta cell toxins. In naturally occurring diabetes, implanted islets might be destroyed by the etiologic agent of the original disease; e.g., virus infection, genetic factors, or autoimmunity. Genetically determined diabetes in obese mice, in fact, is resistant to islet transplantation. Since these mice are hyperinsulinemic and not similar to human juvenile onset diabetes (JOD), more appropriate models were sought, "BB" rats spontaneously develop a syndrome remarkably similar to human JOD. We have studied 279 BB rats. In 31 rats the sudden onset of severe hyperglycemia was observed. Sinc BB rats proved to be AgB2 on serological typing, WF (AgB2) donors were selected. Six hundred Wistar-Furth isolated islets were transplanted intraportally in 10 BB diabetic rats immunosuppressed with antilymphocyte serum. All 10 recipients became normoglycemic, remaining so for 1 to 6 monts. An additional animal model studied was virus-induced diabetes in mice, since viral etiology of human diabetes seems likely. DBA mice receiving encephalomyocarditis virus became severely and persistently diabetic. Eight received syngeneic fetal pancreas to the renal subcapsule and became normoglycemic. Removal of the graft 30 days later demonstrated viable islets histologically and resulted in recurrent diabetes. That virally induced murine diabetes and one spontaneous syndrome in rats which is similar to human JOD responded to beta cell implantation argues that this treatment will be effective in man.
D000818:Animals; D000831:Animals, Newborn; D000961:Antilymphocyte Serum / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000150:complications; D007165:Immunosuppression Therapy; D007267:Injections; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D001786:Blood Glucose