| 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. | |
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MedLine Citation:
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PMID: 21633194 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 (group 1 and group 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. |
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Authors:
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Horatiu V Vinerean; Lawrence S Gazda; Richard D Hall; Barry H Smith |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-01 |
Journal Detail:
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Title: Islets Volume: 3 ISSN: 1938-2022 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-6-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101495366 Medline TA: Islets Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Rogosin Institute-Xenia Division; Xenia, OH USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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