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β-Cell subcellular localization of glucose-stimulated Mn uptake by X-ray fluorescence microscopy: implications for pancreatic MRI.
MedLine Citation:
PMID:  22144025     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Manganese (Mn) is a calcium (Ca) analog that has long been used as a magnetic resonance imaging (MRI) contrast agent for investigating cardiac tissue functionality, for brain mapping and for neuronal tract tracing studies. Recently, we have extended its use to investigate pancreatic β-cells and showed that, in the presence of MnCl(2) , glucose-activated pancreatic islets yield significant signal enhancement in T(1) -weigheted MR images. In this study, we exploited for the first time the unique capabilities of X-ray fluorescence microscopy (XFM) to both visualize and quantify the metal in pancreatic β-cells at cellular and subcellular levels. MIN-6 insulinoma cells grown in standard tissue culture conditions had only a trace amount of Mn, 1.14 ± 0.03 × 10(-11)  µg/µm(2) , homogenously distributed across the cell. Exposure to 2 m m glucose and 50 µ m MnCl(2) for 20 min resulted in nonglucose-dependent Mn uptake and the overall cell concentration increased to 8.99 ± 2.69 × 10(-11)  µg/µm(2) . When cells were activated by incubation in 16 m m glucose in the presence of 50 µ m MnCl(2) , a significant increase in cytoplasmic Mn was measured, reaching 2.57 ± 1.34 × 10(-10)  µg/µm(2) . A further rise in intracellular concentration was measured following KCl-induced depolarization, with concentrations totaling 1.25 ± 0.33 × 10(-9) and 4.02 ± 0.71 × 10(-10)  µg/µm(2) in the cytoplasm and nuclei, respectively. In both activated conditions Mn was prevalent in the cytoplasm and localized primarily in a perinuclear region, possibly corresponding to the Golgi apparatus and involving the secretory pathway. These data are consistent with our previous MRI findings, confirming that Mn can be used as a functional imaging reporter of pancreatic β-cell activation and also provide a basis for understanding how subcellular localization of Mn will impact MRI contrast. Copyright © 2011 John Wiley & Sons, Ltd.
Authors:
Lara Leoni; Anita Dhyani; Patrick La Riviere; Stefan Vogt; Barry Lai; B B Roman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Contrast media & molecular imaging     Volume:  6     ISSN:  1555-4317     ISO Abbreviation:  Contrast Media Mol Imaging     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-12-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101286760     Medline TA:  Contrast Media Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  474-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 John Wiley & Sons, Ltd.
Affiliation:
Department of Radiology, Committee on Medical Physics, University of Chicago, Chicago, IL, USA.
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