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dc.contributor.authorKruger, Annie J.
dc.contributor.authorYang, Chaoxing
dc.contributor.authorLipson, Kathryn L.
dc.contributor.authorPino, Steven C.
dc.contributor.authorLeif, Jean H.
dc.contributor.authorHogan, Christopher M.
dc.contributor.authorWhalen, Barbara J.
dc.contributor.authorGuberski, Dennis L L.
dc.contributor.authorLee, Young
dc.contributor.authorUnger, Roger H.
dc.contributor.authorGreiner, Dale L.
dc.contributor.authorRossini, Aldo A.
dc.contributor.authorBortell, Rita
dc.date2022-08-11T08:08:47.000
dc.date.accessioned2022-08-23T16:08:19Z
dc.date.available2022-08-23T16:08:19Z
dc.date.issued2010-08-09
dc.date.submitted2010-09-16
dc.identifier.issn1607-842X
dc.identifier.pmid20695765
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32419
dc.description.abstractThe 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.
dc.language.isoen_US
dc.publisherTaylor & Francis
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20695765&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.3109/08916934.2010.482116
dc.rightsCitation: Autoimmunity. 2010 Aug 9. [Epub ahead of print]. doi:10.3109/08916934.2010.482116
dc.subjectDiabetes Mellitus, Type 1
dc.subjectLeptin
dc.subjectRats, Inbred BB
dc.subjectIslets of Langerhans Transplantation
dc.subjectNutritional and Metabolic Diseases
dc.titleLeptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats
dc.typeJournal Article
dc.source.journaltitleAutoimmunity
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_mdphd/19
dc.identifier.contextkey1562062
html.description.abstract<p>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.</p>
dc.identifier.submissionpathgsbs_mdphd/19
dc.contributor.departmentDepartment of Medicine, Division of Diabetes
dc.contributor.departmentGraduate School of Biomedical Sciences, MD/PhD Program
dc.contributor.studentAnnie J. Kruger


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