scholarly journals In Vivo Molecular Imaging of Somatostatin Receptors in Pancreatic Islet Cells and Neuroendocrine Tumors by Miniaturized Confocal Laser-Scanning Fluorescence Microscopy

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2179-2188 ◽  
Author(s):  
C. Fottner ◽  
E. Mettler ◽  
M. Goetz ◽  
E. Schirrmacher ◽  
M. Anlauf ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Neuroendocrine Tumors ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Somatostatin Receptors ◽  
Confocal Laser ◽  
Pancreatic Islet Cells ◽  
Specific Time ◽  
Tubular Cells

The aim of the study was to evaluate real time in vivo molecular imaging of somatostatin receptors (sstrs) using a handheld miniaturized confocal laser scan microscope (CLM) in conjunction with fluorescein-labeled octreotate (OcF) in healthy mice and murine models of neuroendocrine tumors. For CLM a small rigid probe (diameter 7 mm) with an integrated single line laser (488 nm) was used (optical slice thickness 7 μm; lateral resolution 0.7 μm). OcF was synthesized via Fmoc solid-phase peptide synthesis and purified by HPLC showing high-affinity binding to the sstr2 (IC50 6.2 nmol). For in vitro evaluation, rat and human pancreatic cancer cells were used and characterized with respect to its sstr subtype expression and functional properties. For in vivo confocal imaging, healthy mouse pancreatic islet and renal tubular cells as well as immunoincompetent nude mice harboring sstr-expressing tumors were evaluated. Incubation of sstr-positive cells with OcF showed a specific time- and dose-dependent staining of sstr-positive cells. CLM showed rapid internalization and homogenous cytoplasmatic distribution. After systemic application to mice (n = 8), specific time-dependent internalization and cytoplasmatic distribution into pancreatic islet cells and tubular cells of the renal cortex was recorded. After injection in tumor-harboring nude mice (n = 8), sstr-positive cells selectively displayed a cell surface and cytoplasmatic staining. CLM-targeted biopsies detected sstr-positive tumor cells with a sensitivity of 87.5% and a specificity of 100% as correlated with ex vivo immunohistochemistry. CLM with OcF permits real-time molecular, functional, and morphological imaging of sstr-expressing cell structures, allowing the specific visualization of pancreatic islet cells and neuroendocrine tumors in vivo.

scholarly journals Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

Diabetologia ◽  
2004 ◽  
Vol 47 (2) ◽  
pp. 225-239 ◽  
Author(s):  
P. Ylipaasto ◽  
K. Klingel ◽  
A. M. Lindberg ◽  
T. Otonkoski ◽  
R. Kandolf ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Pancreatic Islet Cells ◽  
Enterovirus Infection ◽  
Islet Beta Cells ◽  
Human Pancreatic Islet

scholarly journals CXC chemokine ligand 12α-mediated increase in insulin secretion and survival of mouse pancreatic islets in response to oxidative stress through modulation of calcium uptake

2018 ◽  
Vol 70 (1) ◽  
pp. 191-204 ◽  
Author(s):  
Melita Vidakovic ◽  
Ernesto Caballero-Garrido ◽  
Mirjana Mihailovic ◽  
Jelena Arambasic-Jovanovic ◽  
Marija Sinadinovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Diabetes Diagnosis ◽  
Pancreatic Islet Cells ◽  
Pancreatic Cell ◽  
Cxcr4 Signaling

We examined whether CXCL12? improves insulin secretion by influencing the Ca2+ oscillation pattern and Ca2+ influx ([Ca2+]i), thereby enhancing the viability of pancreatic islet cells in oxidative stress. The islets of Langerhans were isolated from male OF1 mice and pretreated with 40 ng/mL of CXCL12? prior to exposure to 7.5 ?M hydrogen peroxide, which served to induce oxidative stress. Incubation of islets with CXCL12? induced pancreatic ?-cell proliferation and improved the ability of ?-cells to withstand oxidative stress. Consecutive treatments of isolated islets with hydrogen peroxide caused a decline in ?-cell functioning over time, while the CXCL12? pretreatment of islets exhibited a physiological response to high glucose that was comparable to control islets. The attenuated response of islets to a high D-glucose challenge was observed as a partial to complete abolishment of [Ca2+]i. Treatments with increasing concentrations of CXCL12? decreased the number of Ca2+ oscillations that lasted longer, thus pointing to an overall increase in [Ca2+]i, which was followed by increased insulin secretion. In addition, treatment of islets with CXCL12? enhanced the transcription rate for insulin and the CXCR4 gene, pointing to the importance of CXCL12/CXCR4 signaling in the regulation of Ca2+ intake and insulin secretion in pancreatic islet cells. We propose that a potential treatment with CXCL12? could help to remove preexisting glucotoxicity and associated temporary ?-cell stunning that might be present at the time of diabetes diagnosis in vivo.

scholarly journals In Vivo ZIMIR Imaging of Mouse Pancreatic Islet Cells Shows Oscillatory Insulin Secretion

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiuhwei Chen ◽  
ZhiJiang Huang ◽  
Harrison Kidd ◽  
Min Kim ◽  
Eul Hyun Suh ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Pancreatic Islet Cells ◽  
Systemic Delivery ◽  
Β Cells ◽  
Spatiotemporal Resolution

Appropriate insulin secretion is essential for maintaining euglycemia, and impairment or loss of insulin release represents a causal event leading to diabetes. There have been extensive efforts of studying insulin secretion and its regulation using a variety of biological preparations, yet it remains challenging to monitor the dynamics of insulin secretion at the cellular level in the intact pancreas of living animals, where islet cells are supplied with physiological blood circulation and oxygenation, nerve innervation, and tissue support of surrounding exocrine cells. Herein we presented our pilot efforts of ZIMIR imaging in pancreatic islet cells in a living mouse. The imaging tracked insulin/Zn2+ release of individual islet β-cells in the intact pancreas with high spatiotemporal resolution, revealing a rhythmic secretion activity that appeared to be synchronized among islet β-cells. To facilitate probe delivery to islet cells, we also developed a chemogenetic approach by expressing the HaloTag protein on the cell surface. Finally, we demonstrated the application of a fluorescent granule zinc indicator, ZIGIR, as a selective and efficient islet cell marker in living animals through systemic delivery. We expect future optimization and integration of these approaches would enable longitudinal tracking of beta cell mass and function in vivo by optical imaging.

Specific Targeting of Pancreatic Islet Cells In Vivo by Insulin-Promoter-Driven Adenoviral Conjugated Reporter Genes

2006 ◽  
Vol 30 (8) ◽  
pp. 1543-1552 ◽  
Author(s):  
Xiaoping Wang ◽  
Elizabeth Olmsted-Davis ◽  
Alan Davis ◽  
Shihe Liu ◽  
Zhijun Li ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Islet Cells ◽  
Reporter Genes ◽  
Pancreatic Islet Cells ◽  
Specific Targeting ◽  
Insulin Promoter

scholarly journals Recent progress in pancreatic islet cell therapy

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Erinn Zixuan Sim ◽  
Nobuaki Shiraki ◽  
Shoen Kume
Keyword(s):  
Stem Cells ◽  
Pancreatic Islet ◽  
Islet Cell ◽  
Recent Progress ◽  
Disease Modeling ◽  
Islet Cells ◽  
Pancreatic Islet Cells ◽  
Pancreatic Islet Cell

AbstractHuman pluripotent stem cells (PSCs), including human embryonic stem cells and induced pluripotent stem cells, are promising cell sources in regenerating pancreatic islets through in vitro directed differentiation. Recent progress in this research field has made it possible to generate glucose-responsive pancreatic islet cells from PSCs. Single-cell RNA sequencing techniques have been applied to analyze PSC-derived endocrine beta-cells, which are then compared with human islets. This has led to the identification of novel signaling pathways and molecules involved in lineage commitment during pancreatic differentiation and maturation processes. Single-cell transcriptomics are also used to construct a detailed map of in vivo endocrine differentiation of developing mouse embryos to study pancreatic islet development. Mimicking those occurring in vivo, it was reported that differentiating PSCs can generate similar islet cell structures, while metabolomics analysis highlighted key components involved in PSC-derived pancreatic islet cell function, providing information for the improvement of in vitro pancreatic maturation procedures. In addition, cell transplantation into diabetic animal models, together with the cell delivery system, is studied to ensure the therapeutic potentials of PSC-derived pancreatic islet cells. Combined with gene-editing technology, the engineered mutation-corrected PSC lines originated from diabetes patients could be differentiated into functional pancreatic islet cells, suggesting possible autologous cell therapy in the future. These PSC-derived pancreatic islet cells are a potential tool for studies of disease modeling and drug testing. Herein, we outlined the directed differentiation procedures of PSC-derived pancreatic islet cells, novel findings through transcriptome and metabolome studies, and recent progress in disease modeling.

Monolayer cultures of adult pancreatic islet cells on osmotically disrupted fibroblasts

Diabetes ◽  
1980 ◽  
Vol 29 (6) ◽  
pp. 497-500 ◽  
Author(s):  
P. Meda ◽  
E. L. Hooghe-Peters ◽  
L. Orci
Keyword(s):  
Pancreatic Islet ◽  
Islet Cells ◽  
Pancreatic Islet Cells ◽  
Monolayer Cultures
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