scholarly journals Establishment of new clonal pancreatic β-cell lines (MIN6-K) useful for study of incretin/cyclic adenosine monophosphate signaling

2010 ◽  
pp. no-no ◽  
Author(s):  
Masahiro Iwasaki ◽  
Kohtaro Minami ◽  
Tadao Shibasaki ◽  
Takashi Miki ◽  
Jun-ichi Miyazaki ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Pancreatic Β Cell ◽  
Β Cell

Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic β-cells

2008 ◽  
Vol 294 (3) ◽  
pp. E540-E550 ◽  
Author(s):  
Elida Lai ◽  
George Bikopoulos ◽  
Michael B. Wheeler ◽  
Maria Rozakis-Adcock ◽  
Allen Volchuk
Keyword(s):  
Er Stress ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Human Islets ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Min6 Cells ◽  
Relative Contribution ◽  
Induced Apoptosis

Chronic exposure to elevated saturated free fatty acid (FFA) levels has been shown to induce endoplasmic reticulum (ER) stress that may contribute to promoting pancreatic β-cell apoptosis. Here, we compared the effects of FFAs on apoptosis and ER stress in human islets and two pancreatic β-cell lines, rat INS-1 and mouse MIN6 cells. Isolated human islets cultured in vitro underwent apoptosis, and markers of ER stress pathways were elevated by chronic palmitate exposure. Palmitate also induced apoptosis in MIN6 and INS-1 cells, although the former were more resistant to both apoptosis and ER stress. MIN6 cells were found to express significantly higher levels of ER chaperone proteins than INS-1 cells, which likely accounts for the ER stress resistance. We attempted to determine the relative contribution that ER stress plays in palmitate-induced β-cell apoptosis. Although overexpressing GRP78 in INS-1 cells partially reduced susceptibility to thapsigargin, this failed to reduce palmitate-induced ER stress or apoptosis. In INS-1 cells, palmitate induced apoptosis at concentrations that did not result in significant ER stress. Finally, MIN6 cells depleted of GRP78 were more susceptible to tunicamycin-induced apoptosis but not to palmitate-induced apoptosis compared with control cells. These results suggest that ER stress is likely not the main mechanism involved in palmitate-induced apoptosis in β-cell lines. Human islets and MIN6 cells were found to express high levels of stearoyl-CoA desaturase-1 compared with INS-1 cells, which may account for the decreased susceptibility of these cells to the cytotoxic effects of palmitate.

IGF-II, IGF-binding proteins and IGF receptors in pancreatic β-cell lines

1997 ◽  
Vol 152 (3) ◽  
pp. 455-464 ◽  
Author(s):  
L E L Katz ◽  
A Bhala ◽  
E Camron ◽  
S E Nunn ◽  
R L Hintz ◽  
...  
Keyword(s):  
Cell Lines ◽  
Binding Proteins ◽  
Conditioned Media ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Igf Binding Proteins ◽  
Igf Receptors ◽  
Igf I ◽  
Igf Binding ◽  
Hit Cells

The IGFs are mitogenic agents which are closely linked to regulatory processes in carbohydrate metabolism. Because limited information is available on the occurrence of the IGF system in the pancreatic β-cell milieu, we evaluated the presence of IGFs, IGF receptors, and IGF-binding proteins (IGFBPs) in the β-cell lines βTC3 and HIT T-15. Serum-free conditioned media (SFCM) from βTC3 cells contained IGF-II at concentrations greater than 100 ng/ml. High (15 kDa) and low (7·5 kDa) molecular weight IGF-II were detected both by column chromatography followed by RIA and by immunoblotting. GH (10–1000 ng/ml) conditioning of βTC3 cells stimulated IGF-II secretion in a dose-dependent manner. IGF-II mRNA was detected in βTC3 cells using Northern blots, and also showed a GH-dependent relationship. IGF-II peptide was detected in SFCM from HIT cells, albeit at lower concentrations. To evaluate the presence of IGF receptors in β-cell lines, affinity cross-linking studies were performed on βTC3 cells, demonstrating type I IGF receptors which bound iodinated IGF-II with high affinity, iodinated IGF-I with lesser affinity, and had minimal appreciable binding to iodinated insulin. Type II IGF receptors were not detected. SFCM from βTC3 and HIT cells was subjected to Western ligand blotting, which disclosed the presence of two major IGFBPs of 29 kDa and 24 kDa, characteristic of IGFBP-2 and IGFBP-4. The identity of the specific IGFBPs was confirmed by immunoprecipitation and Northern blotting. Varying the glucose concentration had no significant effect on the levels of IGFBPs, nor did preconditioning with GH, IGF-I, IGF-II, insulin, or glucagon. Levels of both IGFBPs in βTC3 cell-conditioned media increased in the presence of dexamethasone at concentrations of 10−6 m or greater. In summary, we present evidence that β-cell lines comprise an environment for GH and IGF action. We speculate that IGFs, their receptors and binding proteins function as a complex interactive system which regulates β-cell growth and function. Journal of Endocrinology (1997) 152, 455–464

Cyotomedical therapy for insulinopenic diabetes using microencapsulated pancreatic β cell lines

Life Sciences ◽  
2002 ◽  
Vol 71 (15) ◽  
pp. 1717-1729 ◽  
Author(s):  
Ryo Suzuki ◽  
Naoki Okada ◽  
Hajime Miyamoto ◽  
Tatsunobu Yoshioka ◽  
Kayoko Sakamoto ◽  
...  
Keyword(s):  
Cell Lines ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

2014 ◽  
Vol 223 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Michael Rouse ◽  
Antoine Younès ◽  
Josephine M Egan
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Cell Function ◽  
Human Islets ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pde Inhibitors ◽  
Β Cell Function

Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.

scholarly journals EGF suppresses the expression of miR-124a in pancreatic β cell lines via ETS2 activation through the MEK and PI3K signaling pathways

2019 ◽  
Vol 15 (12) ◽  
pp. 2561-2575 ◽  
Author(s):  
Lin Yang ◽  
Yuansen Zhu ◽  
Delin Kong ◽  
Jiawei Gong ◽  
Wen Yu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Lines ◽  
Pi3k Signaling ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals New α- and SIN γ-retrovectors for safe transduction and specific transgene expression in pancreatic β cell lines

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Olivier Albagli ◽  
Alicia Maugein ◽  
Lukas Huijbregts ◽  
Delphine Bredel ◽  
Géraldine Carlier ◽  
...  
Keyword(s):  
Cell Lines ◽  
Transgene Expression ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic β-Cell Lines

2007 ◽  
Vol 282 (27) ◽  
pp. 19575-19588 ◽  
Author(s):  
Nadine Baroukh ◽  
Magalie A. Ravier ◽  
Merewyn K. Loder ◽  
Elaine V. Hill ◽  
Ali Bounacer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Intracellular Signaling ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Antitumor activity of the dual BET and CBP/EP300 inhibitor NEO2734

2020 ◽  
Vol 4 (17) ◽  
pp. 4124-4135 ◽  
Author(s):  
Filippo Spriano ◽  
Eugenio Gaudio ◽  
Luciano Cascione ◽  
Chiara Tarantelli ◽  
Federica Melle ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Binding Protein ◽  
Single Agent ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Element Binding Protein ◽  
Prostate Cancers

Abstract Bromodomain and extra-terminal domain (BET) proteins, cyclic adenosine monophosphate response element-binding protein (CBP), and the E1A-binding protein of p300 (EP300) are important players in histone acetylation. Preclinical evidence supports the notion that small molecules targeting these proteins individually or in combination can elicit antitumor activity. Here, we characterize the antitumor activity of the pan BET/CBP/EP300 inhibitor NEO2734 and provide insights into its mechanism of action through bromodomain-binding assays, in vitro and in vivo treatments of cancer cell lines, immunoblotting, and transcriptome analyses. In a panel of 60 models derived from different tumor types, NEO2734 exhibited antiproliferative activity in multiple cell lines, with the most potent activity observed in hematologic and prostate cancers. Focusing on lymphoma cell lines, NEO2374 exhibited a pattern of response and transcriptional changes similar to lymphoma cells exposed to either BET or CBP/EP300 inhibitors alone. However, NEO2734 was more potent than single-agent BET or CBP/EP300 inhibitors alone. In conclusion, NEO2734 is a novel antitumor compound that shows preferential activity in lymphomas, leukemias, and prostate cancers.

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