: Type 1 diabetes develops through an initial phase, termed insulitis, which is characterized by leukocytic infiltration of the islets of Langerhans, and slowly evolves to its overt phase, when more than 90% of the b cells have been destroyed and insulin production is insufficient to regulate blood glucose levels As insulitis is asymptomatic, diabetes is often diagnosed during its overt phase and consequently, very little is known about its progression, in humans in particular We propose to test the hypothesis that the stratification of diabetes progression is reflected in physiologic changes occurring in the pancreas We will exploit recent advances in the fields of optical and magnetic resonance imaging (MRI), to develop and optimize novel techniques for the in vivo imaging of pancreatic inflammation These techniques will be established in well-characterized animal models of type 1 diabetes, including the non-obese diabetic (NOD) and the BDC2 5 T cell receptor (TCR) transgenic (tg) models, which exhibit spontaneous diabetes Subsequently, we will apply the developed technology in animal models of type 1 diabetes to address questions regarding the heterogeneity, progression and stratification of the disease and factors that control them. Such information will be invaluable for the detection, prevention and treatment of type 1 diabetes.
| Denis, Maria C; Mahmood, Umar; Benoist, Christophe et al. (2004) Imaging inflammation of the pancreatic islets in type 1 diabetes. Proc Natl Acad Sci U S A 101:12634-9 |
