| 1. |
- Ahlgren, Ulf, et al.
(author)
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Imaging the pancreatic beta cell : chapter 13
- 2011
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In: Type 1 diabetes. - : InTech. - 9789533073620
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Book chapter (peer-reviewed)abstract
- This book is a compilation of reviews about the pathogenesis of Type 1 Diabetes. T1D is a classic autoimmune disease. Genetic factors are clearly determinant but cannot explain the rapid, even overwhelming expanse of this disease. Understanding etiology and pathogenesis of this disease is essential. A number of experts in the field have covered a range of topics for consideration that are applicable to researcher and clinician alike. This book provides apt descriptions of cutting edge technologies and applications in the ever going search for treatments and cure for diabetes. Areas including T cell development, innate immune responses, imaging of pancreata, potential viral initiators, etc. are considered.
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| 2. |
- Eriksson, Anna U., et al.
(author)
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Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research
- 2013
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In: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 71
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Journal article (peer-reviewed)abstract
- By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.
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| 3. |
- Hahn, Max, et al.
(author)
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Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes
- 2020
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In: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.
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| 4. |
- Parween, Saba, et al.
(author)
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Intra-islet lesions and lobular variations in β-cell mass expansion in ob/ob mice revealed by 3D imaging of intact pancreas
- 2016
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- The leptin deficient ob/ob mouse is a widely used model for studies on initial aspects of metabolic disturbances leading to type 2 diabetes, including insulin resistance and obesity. Although it is generally accepted that ob/ob mice display a dramatic increase in β-cell mass to compensate for increased insulin demand, the spatial and quantitative dynamics of β-cell mass distribution in this model has not been assessed by modern optical 3D imaging techniques. We applied optical projection tomography and ultramicroscopy imaging to extract information about individual islet β-cell volumes throughout the volume of ob/ob pancreas between 4 and 52 weeks of age. Our data show that cystic lesions constitute a significant volume of the hyperplastic ob/ob islets. We propose that these lesions are formed by a mechanism involving extravasation of red blood cells/plasma due to increased islet vessel blood flow and vessel instability. Further, our data indicate that the primary lobular compartments of the ob/ob pancreas have different potentials for expanding their β-cell population. Unawareness of the characteristics of β-cell expansion in ob/ob mice presented in this report may significantly influence ex vivo and in vivo assessments of this model in studies of β-cell adaptation and function.
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| 5. |
- Parween, Saba, et al.
(author)
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Spatial and quantitative datasets of the pancreatic beta-cell mass distribution in lean and obese mice
- 2017
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Journal article (peer-reviewed)abstract
- A detailed understanding of pancreatic β-cell mass distribution is a key element to fully appreciate the pathophysiology of models of diabetes and metabolic stress. Commonly, such assessments have been performed by stereological approaches that rely on the extrapolation of two-dimensional data and provide very limited topological information. We present ex vivo optical tomographic data sets of the full β-cell mass distribution in cohorts of obese ob/ob mice and their lean controls, together with information about individual islet β-cell volumes, their three-dimensional coordinates and shape throughout the volume of the pancreas between 4 and 52 weeks of age. These data sets offer the currently most comprehensive public record of the β-cell mass distribution in the mouse. As such, they may serve as a quantitative and topological reference for the planning of a variety of in vivo or ex vivo experiments including computational modelling and statistical analyses. By shedding light on intra- and inter-lobular variations in β-cell mass distribution, they further provide a powerful tool for the planning of stereological sampling assessments.
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