Year: 2014
Type: dissertation
Abstract: Type 1 diabetes (T1D) is an immune-mediated disease characterized by autoimmune inflammation (insulitis), leading to destruction of insulin-producing pancreatic β-cells and consequent dependence on exogenous insulin.Current evidence suggests that T1D arises in genetically susceptible children who are exposed to poorly characterized environmental triggers.Investigations largely focus on identifying patients at risk for T1D and slowing the β-cell destruction.Advances in positron emission tomography (PET) imaging have enabled the development of radiotracers for imaging insulitis, and assessing pancreatic β-cells.Here the use of 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) was evaluated for in vivo imaging of insulitis in both mice and T1D patients.Radioactivity uptake was up to 2.3 times higher in insulitis-affected islets of NOD mice compared to unaffected islets within the same pancreas or islets of healthy control mice.The findings of this thesis also demonstrated that the glucose uptake in the human pancreas measured by [ 18 F]FDG PET was inversely associated with the duration of diabetes.Patients with newly diagnosed T1D showed higher uptake than healthy controls or patients with a long duration of diabetes.We further evaluated 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine ([ 18 F]FDOPA) uptake in the healthy rat pancreas for visualization of β-cells after treatment with several enzymatic inhibitors.The pancreas exhibited increased radioactivity uptake and changes in the radiometabolic profile, allowing better discrimination between the pancreas and surrounding tissues of the rat.However, these manipulations were insufficient to separate islets from the exocrine pancreas.
Source: UTUPub (University of Turku)
Author: Teemu Kalliokoski
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W44723802