Finally LC ESI MS MS was applied to explore
Finally, LC-ESI-MS/MS was applied to explore the effects of increased fT4 levels 4 and 8 weeks after induced thyrotoxicosis and have revealed an upregulation of proteins involved in blood coagulation, thus providing a clear association .
Introduction Diabetes mellitus (DM) has laid tremendous pressures on healthcare systems worldwide . In 2001, the prevalence of youth with type 1 ER 27319 maleate receptor (T1DM) in the U.S. was 1.48 per 1000, increasing to 1.93 per 1000 in 2009, a 21% increase between 2001 and 2009 after adjustment . The World Health Organization estimated that there were 422 million adults over 18 years of age living with all types of diabetes in 2014, which was four times higher than that in 1980 (the number at that time was 108 million) . It is expected that over 550 million people will be diagnosed with diabetes by 2030 . Diabetic disorders can be broadly divided into four groups: type 1, type 2, gestational, or a group of other specific syndromes . T1DM, as an autoimmune disorder, results from immune-mediated destruction of insulin-producing β-cells, while type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with insulin desensitization or resistance, which occurs at multiple levels of the insulin receptors on different cell types [, , ]. There is growing evidence indicating a significant overlap across these two different types of diabetes, as both T1DM and T2DM have been associated with a functional loss of beta cell mass (β-cell mass, BCM) . Specifically, BCM was reported to be reduced in patients with T2DM . Hyperglycemia may trigger a stress response which plays a role in the induction of β-cell apoptosis in both T1DM and T2DM . Hyperglycemia seems to be associated with changes in β-cell phenotype, such as dedifferentiation of β-cells, which is important to the development of diabetes . Therefore, an insufficient number and/or functional decline of β-cells have been determined to be central components in the development and progression of hyperglycemia and diabetes. Currently only circulating C-peptide and insulin levels are relatively reliable approaches to measure BCM. However, these two methods still lack sensitivity and reproducibility, as these indexes only indirectly reflect BCM and are not able to determine the changes in BCM amounts [5,13]. From a clinical perspective, early detection of β-cell changes is key to timely diagnosis and intervention of diabetes, such as in initial stages of the disease or in the β-cell compensation phase (when glucose levels are not elevated). Therefore, sensitive new tools that can noninvasively map BCM are urgently needed. β-cell imaging is one of the most optimal candidates . While in people affected by T1DM the value of β-cell specific imaging may lie in detecting almost complete loss of BCM, in people with T2DM, β-cell imaging techniques can be applied to monitor the subtle changes of BCM over longer time periods [, , , ]. 18F-FDG, the most commonly-used positron emission tomography (PET) tracer, has been employed to delineate transplanted islets and to assess the mass of β-cells in streptozotocin (STZ)-induced diabetic rats . Although 18F-FDG-labeled islets allowed qualitative and quantitative analysis of transplanted islets , the role of 18F-FDG in monitoring BCM was controversial as it failed to accumulate less in the diabetic pancreas compared to the control . Therefore, 18F-FDG PET/CT may hold potential in monitoring islet transplantation; however, this technique faces a number of challenges, including the need for pretreatment of islets, minimal sensitivity for small islet losses, and the relatively short half-life of 18F . The need for noninvasive and quantitative assessment of BCM has prompted the development of many β-cell-specific imaging agents targeting the vesicular monoamine transporter 2 (VMAT2), sulphonylurea receptors (SUR-1), glucagon-like peptide 1 (GLP-1), free fatty acid receptor 1 (FFAR1), and β-cell-specific antigens [16,17,23]. Of them, Mn-DPDP , 11C-DTBZ , 18F-AV-133 , 18F-FDOPA , and 68Ga-NOTA-exendin-4  are representative probes which have been tested in clinical settings and have shown great promise for evaluating BCM. Several imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI), PET, single-photon emission computed tomography (SPECT), and optical imaging have been explored for noninvasive detection and measurement of BCM and β-cell function. In the past, Wu and others elaborately prepared reviews of radionuclide-based molecular imaging probes for β-cells [15,17,22]; since then, substantial molecular imaging probes for various targets have been developed and investigated for diabetes or other β-cell related conditions (i.e., insulinomas and islet transplantation). By reviewing the most recent reports and highlighting remaining research gaps, we herein systematically summarize potential molecular probes for imaging β-cells (Fig. 1), and we believe that β-cell imaging will lead to tailored diagnostic tools and development of personalized medicine for patients with diabetes and insulinomas in the near future.