Title

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

Student Author(s)

Annie J. Kruger

UMMS Affiliation

Graduate School of Biomedical Sciences, MD/PhD Program; Department of Medicine, Division of Diabetes

Date

8-9-2010

Document Type

Article

Medical Subject Headings

Diabetes Mellitus, Type 1; Leptin; Rats, Inbred BB; Islets of Langerhans Transplantation

Abstract

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.

Rights and Permissions

Citation: Autoimmunity. 2010 Aug 9. [Epub ahead of print]. doi:10.3109/08916934.2010.482116

Related Resources

Link to article in PubMed

PubMed ID

20695765