exendin-3 and Diabetes-Mellitus--Type-1

Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the β cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice.. NOD mice (. The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson. Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.

Topics: Animals; Autoradiography; Diabetes Mellitus, Type 1; Disease Models, Animal; Female; Hyperglycemia; Immunohistochemistry; Indium Radioisotopes; Injections, Intravenous; Insulin-Secreting Cells; Mice; Mice, Inbred NOD; Pentetic Acid; Peptides; Radiopharmaceuticals; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of

Topics: Animals; Diabetes Mellitus, Type 1; Female; Humans; Indium Radioisotopes; Insulin-Secreting Cells; Peptides; Rats; Tomography, Emission-Computed, Single-Photon

Islet transplantation is a novel promising strategy to cure type 1 diabetes. However, the long-term outcome is still poor, because both function and survival of the transplant decline over-time. Non-invasive imaging methods have the potential to enable monitoring of islet survival after transplantation and the effects of immunosuppressive drugs on transplantation outcome. (111)In-labeled exendin-3 is a promising tracer to visualize native and transplanted islets by SPECT (Single Photon Emission Computed Tomography). In the present study, we hypothesized that islet microvasculature plays an important role determining the uptake of exendin-3 in islets when monitoring transplant survival. We observed (111)In-exendin-3 accumulation in the transplant as early as three days after transplantation and an increase in the uptake up to three weeks post-transplantation. Islet-revascularization correlated with the increase in (111)In-exendin-3 uptake, whereas fully re-established islet vasculature coincided with a stabilized uptake of the radiotracer in the transplant. Here, we demonstrate the importance of islet vasculature for in vivo delivery of radiotracers to transplanted islets and we demonstrate that optimal and stable uptake of exendin four weeks after transplantation opens the possibility for long-term monitoring of islet survival by SPECT imaging.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Graft Survival; Humans; Indium Radioisotopes; Islets of Langerhans Transplantation; Mice; Peptides; Radiography; Tomography, Emission-Computed, Single-Photon