Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats

• DOI: 10.3109/08916934.2010.482116
• Publication Date: 2010-08-09T10:36:08Z
• Authors: 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
• Keywords: Insulitis

The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that dual effects leptin may prevent or suppress autoreactive destruction cells in a virally induced rodent model type 1 diabetes. Nearly 100% weanling BBDR rats treated with combination an innate system activator, polyinosinic:polycytidylic acid (pIC), Kilham rat virus (KRV) become diabetic within predictable time frame. utilized this to test efficacy preventing diabetes onset, remitting new onset disease, autoimmune recurrence transplanted syngeneic islet grafts. High doses delivered via adenovirus vector (AdLeptin) alzet pump prevented in>90% pIC+KRV. serum hyperleptinemia generated by treatment was associated decreased body weight, non-fasting levels, lack insulitis leptin-treated rats. In diabetics, rapid weight loss ketoacidosis, temporarily restored euglycemia. Leptin prolonged survival islets into diverse therapeutic settings, we found have significant beneficial These findings merit further evaluation as potential adjunct agent for human