High-Throughput FRET Assays for Fast Time-Dependent Detection of Cyclic AMP in Pancreatic β Cells

2015 ◽  
pp. 52-77 ◽  
Keyword(s):  
Cyclic Amp ◽  
High Throughput ◽  
Time Dependent ◽  
Fast Time ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Silymarin Protects Pancreatic β-Cells against Cytokine-Mediated Toxicity: Implication of c-Jun NH2-Terminal Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Pathways

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 175-185 ◽  
Author(s):  
Takeru Matsuda ◽  
Kevin Ferreri ◽  
Ivan Todorov ◽  
Yoshikazu Kuroda ◽  
Craig V. Smith ◽  
...  
Keyword(s):  
Cell Death ◽  
Human Islets ◽  
Janus Kinase ◽  
Time Dependent ◽  
No Production ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Ifn Γ

Silymarin is a polyphenolic flavonoid that has a strong antioxidant activity and exhibits anticarcinogenic, antiinflammatory, and cytoprotective effects. Although its hepatoprotective effect has been well documented, the effect of silymarin on pancreatic β-cells is largely unknown. In this study, the effect of silymarin on IL-1β and/or interferon (IFN)-γ-induced β-cell damage was investigated using RINm5F cells and human islets. IL-1β and/or IFN-γ induced cell death in a time-dependent manner in RINm5F cells. The time-dependent increase in cytokine-induced cell death appeared to correlate with the time-dependent nitric oxide (NO) production. Silymarin dose-dependently inhibited both cytokine-induced NO production and cell death in RINm5F cells. Treatment of human islets with a combination of IL-1β and IFN-γ (IL-1β+IFN-γ), for 48 h and 5 d, resulted in an increase of NO production and the impairment of glucose-stimulated insulin secretion, respectively. Silymarin prevented IL-1β+IFN-γ-induced NO production and β-cell dysfunction in human islets. These cytoprotective effects of silymarin appeared to be mediated through the suppression of c-Jun NH2-terminal kinase and Janus kinase/signal transducer and activator of transcription pathways. Our data show a direct cytoprotective effect of silymarin in pancreatic β-cells and suggest that silymarin may be therapeutically beneficial for type 1 diabetes.

scholarly journals Recent advances and potential applications of human pluripotent stem cell-derived pancreatic β cells

2020 ◽  
Vol 52 (7) ◽  
pp. 708-715 ◽  
Author(s):  
Ziyu Zhou ◽  
Xiaojie Ma ◽  
Saiyong Zhu
Keyword(s):  
High Throughput ◽  
Disease Modeling ◽  
Patient Specific ◽  
Target Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
High Blood Glucose ◽  
Chemical Screening ◽  
Recent Advances ◽  
Potential Applications

Abstract Diabetes mellitus is characterized by chronic high blood glucose levels resulted from deficiency and/or dysfunction of insulin-producing pancreatic β cells. Generation of large amounts of functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes. Recent advances in directed differentiation of pancreatic β-like cells from human pluripotent stem cells (hPSCs) can provide patient-specific and disease-relevant target cells. With the improved differentiation protocols, it is now possible to generate large amounts of functional human pancreatic β-like cells that can response to high level of glucose both in vitro and in vivo. Combined with precise genomic editing, biomedical engineering, high throughput profiling, bioinformatics, and high throughput genetic and chemical screening, these hPSC-derived pancreatic β-like cells will hold great potentials in disease modeling, drug discovery, and cell-based therapies. In this review, we summarize the recent progress in human pancreatic β-like cells derived from hPSCs and discuss their potential applications.

scholarly journals Overexpression of Inducible Cyclic AMP Early Repressor Inhibits Transactivation of Genes and Cell Proliferation in Pancreatic β Cells

2004 ◽  
Vol 24 (7) ◽  
pp. 2831-2841 ◽  
Author(s):  
Akari Inada ◽  
Yoshiyuki Hamamoto ◽  
Yoshiyuki Tsuura ◽  
Jun-ichi Miyazaki ◽  
Shinya Toyokuni ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Transcriptional Control ◽  
Cell Mass ◽  
Cyclin A ◽  
Postnatal Period ◽  
Cell Physiology ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Transgenic Lines

ABSTRACT Transcriptional control mediated by the cyclic AMP-responsive element (CRE) represents an important mechanism of gene regulation. To test our hypothesis that increased inducible cyclic AMP early repressor (ICER) Iγ inhibits function of CRE-binding proteins and thus disrupts CRE-mediated transcription in pancreatic β cells, we generated transgenic mice with β-cell-directed expression of ICER Iγ, a powerful repressor that is greatly increased in diabetes. Three transgenic lines clearly show that increased ICER Iγ expression in β cells results in early severe diabetes. From birth islets were severely disorganized with a significantly increased proportion of α cells throughout the islet. Diabetes results from the combined effects of impaired insulin expression and a decreased number of β cells. The decrease in β cells appears to result from impaired proliferation rather than from increased apoptosis after birth. Cyclin A gene expression is impaired by the strong inhibition of ICER; the suppression of cyclin A results in a substantially decreased proliferation of β cells in the postnatal period. These results suggest that CRE and CRE-binding factors have an important role in pancreatic β-cell physiology not only directly by regulation of gene trans-activation but also indirectly by regulation of β-cell mass.

scholarly journals Glucose Evokes Rapid Ca2+ and Cyclic AMP Signals by Activating the Cell-Surface Glucose-Sensing Receptor in Pancreatic β-Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0144053 ◽  
Author(s):  
Yuko Nakagawa ◽  
Masahiro Nagasawa ◽  
Johan Medina ◽  
Itaru Kojima
Keyword(s):  
Cyclic Amp ◽  
Cell Surface ◽  
Glucose Sensing ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion

PLoS ONE ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. e5106 ◽  
Author(s):  
Yuko Nakagawa ◽  
Masahiro Nagasawa ◽  
Satoko Yamada ◽  
Akemi Hara ◽  
Hideo Mogami ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cyclic Amp ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Signaling Systems ◽  
Sweet Taste Receptor ◽  
Cyclic Amp Signaling

MICROCHEMICAL ASSAYS OF GLUCOSE AND GLUCOSE-6-PHOSPHATE IN MAMMALIAN PANCREATIC β-CELLS

1968 ◽  
Vol 59 (3) ◽  
pp. 479-486 ◽  
Author(s):  
Lars-Ake Idahl ◽  
Bo Hellman
Keyword(s):  
Glucose Level ◽  
Exocrine Pancreas ◽  
The Other ◽  
Wide Concentration Range ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Enzymatic Cycling ◽  
Glucose Diffusion ◽  
Significant Barrier ◽  
The Brain

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.

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