Streptozotocin is responsible for the induction and progression of renal tumorigenesis in diabetic wistar-furth rats treated with insulin or transplanted with agarose encapsulated porcine islets

Abstract

Streptozotocin (STZ), a nitrosourea with DNA alkylating properties, has been widely used to induce hyperglycemia by specifically destroying the insulin-producing β-cells of the islets of Langerhans in experimental models of Type I diabetes. STZ's known carcinogenic properties, however, raise concerns about its suitability for long-term studies. We conducted a formal study of STZ's carcinogenic effects in long-term surviving diabetic Wistar-Furth rats. To determine if insulin therapy or islet transplantation exacerbated tumorigenesis, rats were randomly assigned to one of four experimental groups: normal animals with no treatment (Group 1, n = 12); normal animals that underwent peritoneal implantation of porcine islets encapsulated in a double layer of agarose to form islet macrobeads (Normal + Islets; Group 2, n = 12); STZ treatment followed by daily exogenous insulin (STZ + insulin; Group 3, n = 18) and STZ treatment followed by the intraperitoneal implantation of porcine islet macrobeads (STZ + Islets; Group 4, n = 14). At 215 days post-STZ induction, no renal proliferative lesions were observed in animals that did not receive STZ (Groups 1 and 2) whereas adenoma incidences of 57% for Group 3 and 34% for Group 4 were observed. By terminal necropsy at day 351, the incidence and severity of renal proliferative lesions increased with tubular carcinoma observed in 67% of Group 3 and 60% of Group 4 animals. We conclude that the STZ-induced diabetic rat model is not suitable for long-term studies because of progressive renal tumorigenesis. Our experiments also demonstrate the safety and effectiveness of porcine islet macrobeads for the treatment of diabetes. ©2011 Landes Bioscience.