| Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. | |
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MedLine Citation:
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PMID: 20695765 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes. |
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Authors:
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Annie J Kruger; Chaoxing Yang; Kathryn L Lipson; Stephen C Pino; Jean H Leif; Christopher M Hogan; Barbara J Whalen; Dennis L Guberski; Young Lee; Roger H Unger; Dale L Greiner; Aldo A Rossini; Rita Bortell |
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Publication Detail:
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Type: Journal Article Date: 2010-08-09 |
Journal Detail:
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Title: Autoimmunity Volume: 44 ISSN: 1607-842X ISO Abbreviation: Autoimmunity Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-01-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8900070 Medline TA: Autoimmunity Country: England |
Other Details:
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Languages: eng Pagination: 137-48 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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