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.

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.

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro

2002 ◽  
Vol 25 (5) ◽  
pp. 436-441 ◽  
Author(s):  
F. J. Tinahones ◽  
A. Pareja ◽  
F. J. Soriguer ◽  
J. M. Gómez-Zumaquero ◽  
F. Cardona ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Dietary Fatty Acids ◽  
Pancreatic Islet Cells ◽  
Rat Pancreatic Islet

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

Carbamoylcholine regulation of polyphosphoinositide synthesis and hydrolysis in cultured, dispersed, digitonin-permeabilized mouse pancreatic islet cells

1997 ◽  
Vol 136 (5) ◽  
pp. 539-545 ◽  
Author(s):  
Andrew M Kardasz ◽  
Peter Thams ◽  
Kirsten Capito ◽  
Carl J Hedeskov
Keyword(s):  
Pancreatic Islet ◽  
Kinase Activity ◽  
Inositol Phosphates ◽  
Islet Cells ◽  
Pancreatic Islet Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mouse Pancreatic Islet ◽  
Phosphatidylinositol 4 ◽  
Stimulation Of

Abstract Continuing formation of inositol phosphates during stimulation of pancreatic β-cells by hormones and neurotransmitters requires the continued synthesis of the polyphosphoinositides phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5 bisphosphate (PIP2) from phosphatidylinositol (PI). In the present study we have investigated how this pathway and the activity of phosphoinositide-specific phospholipase C (PI-PLC) are regulated by carbamoylcholine (CCh), Ca2+, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), GTPγS and NaF in 44-h [3H]inositol-labelled, dispersed and digitonin-permeabilized mouse pancreatic islet cells. CCh stimulated not only PI-PLC (G-protein-mediated) but also, by an as yet unknown mechanism, significantly enhanced PI 4-kinase activity, estimated as the PIP:PI ratio, by 100%, and further increased the flux from PI to PIP and PIP2. GTPγS and NaF mimicked the effects of CCh on PI-PLC but had no effect on the levels of PIP and PIP2. TPA raised the PIP:PI ratio by 75%. In addition TPA counteracted the CCh stimulation of PI-PLC. There was no effect of 10−6 mol/l Ca2+ on the levels of PIP and PIP2. Experiments with quinacrine and adenosine confirmed that PI-PLC and PI 4-kinase could be regulated independently of each other. In conclusion, these data point to differential regulation of polyphosphoinositide synthesis and breakdown. European Journal of Endocrinology 136 539–545

scholarly journals Perilipin2 down-regulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria

2020 ◽  
Author(s):  
Akansha Mishra ◽  
Siming Liu ◽  
Joseph Promes ◽  
Mikako Harata ◽  
William Sivitz ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Islet Cells ◽  
Cell Metabolism ◽  
Nutritional Stress ◽  
Β Cells ◽  
Β Cell ◽  
Down Regulation

Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet cells. β cell specific deletion of PLIN2 in mice on a high fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Down-regulation of PLIN2 in INS1 cells blunted GSIS after 24 h incubation with 0.2 mM palmitic acids. Down-regulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Down-regulation of PLIN2 decreased specific OXPHOS proteins in all three models and reduced oxygen consumption rates in INS1 cells and mouse islets. Moreover, we found that PLIN2 deficient INS1 cells increased the distribution of a fluorescent oleic acid analog to mitochondria and showed signs of mitochondrial stress as indicated by susceptibility to fragmentation and alterations of acyl-carnitines and glucose metabolites. Collectively, PLIN2 in β cells have an important role in preserving insulin secretion, β cell metabolism and mitochondrial function under nutritional stress.

scholarly journals LIM-Homeodomain Transcription Factor Isl-1 Mediates Kisspeptin's Effect on Insulin Secretion in Mice

2014 ◽  
Vol 28 (8) ◽  
pp. 1276-1290 ◽  
Author(s):  
Juan Chen ◽  
Rui Fu ◽  
Yan Cui ◽  
Jirong Pan ◽  
Yushan Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Direct Action ◽  
Janus Kinase ◽  
Homeodomain Transcription Factor ◽  
Lim Homeodomain

Kisspeptin and the G protein-coupled receptor 54 (GPR54) are highly abundant in the pancreas. In addition, circulating kisspeptin directly influences insulin secretion through GPR54. However, the mechanisms by which kisspeptin affects insulin release are unclear. The LIM-homeodomain transcription factor, Isl-1, is expressed in all pancreatic islet cells and is involved in regulating both islet development and insulin secretion. We therefore investigated potential interactions between kisspeptin and Isl-1. Our results demonstrate that Isl-1 and GPR54 are coexpressed in mouse pancreatic islet β-cells and NIT cells. Both in vitro and in vivo results demonstrate that kisspeptin-54 (KISS-54) inhibits Isl-1 expression and insulin secretion and both the in vivo and in vitro effects of KISS-54 on insulin gene expression and secretion are abolished when an Isl-1-inducible knockout model is used. Moreover, our results demonstrate that the direct action of KISS-54 on insulin secretion is mediated by Isl-1. Our results further show that KISS-54 influences Isl-1 expression and insulin secretion through the protein kinase C-ERK1/2 pathway. Conversely, insulin has a feedback loop via the Janus kinase-phosphatidylinositol 3-kinase pathway regulating kisspeptin expression and secretion. These findings are important in understanding mechanisms of insulin secretion and metabolism in diabetes.

Sign in / Sign up

Export Citation Format

Share Document