scholarly journals The Protective Role of Calbindin-D9k on Endoplasmic Reticulum Stress-Induced Beta Cell Death

2019 ◽  
Vol 20 (21) ◽  
pp. 5317
Author(s):  
Changhwan Ahn ◽  
Eui-Man Jung ◽  
Beum-Soo An ◽  
Eui-Ju Hong ◽  
Yeong-Min Yoo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Beta Cell ◽  
Er Stress ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death ◽  
Calbindin D9k ◽  
Islet Volume

Intracellular calcium ion content is tightly regulated for the maintenance of cellular functions and cell survival. Calbindin-D9k (CaBP-9k) is responsible for regulating the distribution of cytosolic free-calcium ions. In this study, we aimed to investigate the effect of CaBP-9k on cell survival in pancreatic beta cells. Six-month-old wildtype CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice were used to compare the pathological phenotypes of calcium-binding protein-deleted mice. Subsequently, the endoplasmic reticulum (ER) stress reducer tauroursodeoxycholic acid (TUDCA) was administered to wildtype and CaBP-9k KO mice. In vitro assessment of the role of CaBP-9k was performed following CaBP-9k overexpression and treatment with the ER stress inducer thapsigargin. Six-month-old CaBP-9k KO mice showed reduced islet volume and up-regulation of cell death markers resulting from ER stress, which led to pancreatic beta cell death. TUDCA treatment recovered islet volume, serum insulin level, and abdominal fat storage by CaBP-9k ablation. CaBP-9k overexpression elevated insulin secretion and recovered thapsigargin-induced ER stress in the INS-1E cell line. The results of this study show that CaBP-9k can protect pancreatic beta cell survival from ER stress and contribute to glucose homeostasis, which can reduce the risk of type 1 diabetes and provide the molecular basis for calcium supplementation to diabetic patients.

scholarly journals Role of apoptosis in pancreatic beta-cell death in diabetes

Diabetes ◽  
2001 ◽  
Vol 50 (Supplement 1) ◽  
pp. S44-S47 ◽  
Author(s):  
J. Chandra ◽  
B. Zhivotovsky ◽  
S. Zaitsev ◽  
L. Juntti-Berggren ◽  
P. Berggren ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death

scholarly journals The Class I Histone Deacetylase Inhibitor MS-275 Prevents Pancreatic Beta Cell Death Induced by Palmitate

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Valérie Plaisance ◽  
Laure Rolland ◽  
Valéry Gmyr ◽  
Jean-Sébastien Annicotte ◽  
Julie Kerr-Conte ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Er Stress ◽  
Beta Cells ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Activating Transcription Factor 3 ◽  
Beta Cell Death ◽  
Stress Markers

Elevation of the dietary saturated fatty acid palmitate contributes to the reduction of functional beta cell mass in the pathogenesis of type 2 diabetes. The diabetogenic effect of palmitate is achieved by increasing beta cell death through induction of the endoplasmic reticulum (ER) stress markers including activating transcription factor 3 (Atf3) and CAAT/enhancer-binding protein homologous protein-10 (Chop). In this study, we investigated whether treatment of beta cells with the MS-275, a HDAC1 and HDAC3 activity inhibitor which prevents beta cell death elicited by cytokines, is beneficial for combating beta cell dysfunction caused by palmitate. We show that culture of isolated human islets and MIN6 cells with MS-275 reduced apoptosis evoked by palmitate. The protective effect of MS-275 was associated with the attenuation of the expression of Atf3 and Chop. Silencing of HDAC3, but not of HDAC1, mimicked the effects of MS-275 on the expression of the two ER stress markers and apoptosis. These data point to HDAC3 as a potential drug target for preserving beta cells against lipotoxicity in diabetes.

Perinatal exposure to silver nanoparticles reprograms immunometabolism and promotes pancreatic beta-cell death and kidney damage in mice

2021 ◽  
pp. 1-25
Author(s):  
Ratnakar Tiwari ◽  
Radha Dutt Singh ◽  
Monika Binwal ◽  
Anurag Kumar Srivastav ◽  
Neha Singh ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cell Death ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Kidney Damage ◽  
Perinatal Exposure ◽  
Beta Cell Death

c-Jun Inhibits Thapsigargin-Induced ER Stress Through Up-Regulation of DSCR1/Adapt78

2008 ◽  
Vol 233 (10) ◽  
pp. 1289-1300 ◽  
Author(s):  
Peng Zhao ◽  
Xiaoyan Xiao ◽  
Agnes S. Kim ◽  
M. Fatima Leite ◽  
Jinxia Xu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Wild Type Mouse ◽  
Mouse Fibroblast ◽  
Expression Levels ◽  
Mouse Fibroblasts ◽  
The Unfolded Protein Response ◽  
Calcineurin Activity

The endoplasmic reticulum (ER) is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed “ER stress”, can perturb ER function, leading to the activation of a complex response known as the unfolded protein response (UPR). Although c-Jun N-terminal kinase (JNK) activation is nearly always associated with cell death by various stimuli, the functional role of JNK in ER stress-induced cell death remains unclear. JNK regulates gene expression through the phosphorylation and activation of transcription factors, such as c-Jun. Here, we investigated the role of c-Jun in the regulation of ER stress-related genes. c-Jun expression levels determined the response of mouse fibroblasts to ER stress induced by thapsigargin (TG, an inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase). c-jun−/− mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts, while reconstitution of c-Jun expression in c-jun−/− cells (c-Jun Re) enhanced resistance to TG-induced cell death. The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-Jun Re than in c-jun−/− cells. Moreover, TG treatment significantly increased calcineurin activity in c-jun−/− cells, but not in c-Jun Re cells. In c-Jun Re cells, TG induced the expression of Adapt78, also known as the Down syndrome critical region 1 (DSCR1), which is known to block calcineurin activity. Taken together, our findings suggest that c-Jun, a transcription factor downstream of the JNK signaling pathway, up-regulates Adapt78 expression in response to TG-induced ER stress and contributes to protection against TG-induced cell death.

W46 ROLE OF LIPOPROTEINS IN PANCREATIC BETA-CELL SURVIVAL, PROLIFERATION AND FUNCTION

2010 ◽  
Vol 11 (2) ◽  
pp. 10
Author(s):  
R.A. Sibler ◽  
S. Rütti ◽  
J.A. Ehses ◽  
R. Prazak ◽  
D.T. Meier ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell ◽  
And Function

Nitric oxide and neuronal and pancreatic beta cell death

Toxicology ◽  
2000 ◽  
Vol 153 (1-3) ◽  
pp. 143-156 ◽  
Author(s):  
E Adeghate ◽  
S.H Parvez
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death

scholarly journals APPL1 prevents pancreatic beta cell death and inflammation by dampening NFκB activation in a mouse model of type 1 diabetes

Diabetologia ◽  
2016 ◽  
Vol 60 (3) ◽  
pp. 464-474 ◽  
Author(s):  
Xue Jiang ◽  
Yawen Zhou ◽  
Kelvin K. L. Wu ◽  
Zhanrui Chen ◽  
Aimin Xu ◽  
...  
Keyword(s):  
Cell Death ◽  
Type 1 Diabetes ◽  
Mouse Model ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death

scholarly journals The role of caspase-8 in amyloid-induced beta cell death in human and mouse islets

Diabetologia ◽  
2014 ◽  
Vol 57 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Yoo Jin Park ◽  
Minna Woo ◽  
Timothy J. Kieffer ◽  
Razqallah Hakem ◽  
Nooshin Safikhan ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Caspase 8 ◽  
Beta Cell Death ◽  
Mouse Islets ◽  
Human And Mouse
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