Objective
To elucidate the impact of the peptide hormone in the onset of T1D, we will treat female NOD mice with the peptide hormone and monitor the development of T1D. Histological and immunohistochemical assessment of pancreas samples will be conducted from treated and control NOD mice to monitor islet integrity and insulitis.
Background Rationale
G protein coupled receptors are expressed in pancreatic islets that bind peptide hormones. Some peptide hormones can directly stimulate glucose stimulated insulin secretion from pancreatic beta cells in many species. Furthermore, administration of a specific peptide hormone improves glucose homeostasis in high fat diet fed insulin-resistant mice models of T2D. We will investigate whether this peptide hormone is implicated in the development of Type 1 diabetes.
Description of Project
The objective of our study is to determine whether a peptide hormone that circulates in the blood and is a regulator of the reproductive axis, can delay the onset of diabetes in NOD mice, a model for human type 1 diabetes, without the use of immunosuppressive drugs.
Anticipated Outcome
We anticipate that treatment of the NOD mice with the peptide hormone will increase serum insulin levels and decrease insulitis, thus delaying the onset of T1D compared to controls.
Relevance to T1D
The significance of this work to type 1 diabetes is that it could provide proof-of-concept data for clinical trials using the peptide hormone, to restore normoglycemia. This peptide hormone has been used in clinical studies in children and adults, without toxic effects and thus could rapidly move to treatment of T1D.