scholarly journals Activation of Extracellular Signal-Regulated Protein Kinases 1 and 2 (ERK1/2) by Free Fatty Acid Receptor 1 (FFAR1/GPR40) Protects from Palmitate-Induced Beta Cell Death, but Plays no Role in Insulin Secretion

2015 ◽  
Vol 35 (4) ◽  
pp. 1537-1545 ◽  
Author(s):  
Madhura Panse ◽  
Felicia Gerst ◽  
Gabriele Kaiser ◽  
Charlott-Amélie Teutsch ◽  
Rebecca Dölker ◽  
...  
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Prolonged Exposure ◽  
Underlying Mechanism ◽  
Tunel Staining ◽  
Western Blots ◽  
Beta Cell Death ◽  
Stimulation Of

Aims: GPR40/FFAR1 mediates palmitate-induced stimulation of insulin secretion but its involvement in lipotoxicity is controversial. Our previous observations suggest that FFAR1/GPR40 agonists protect against lipotoxicity although the underlying mechanism remains elusive. The present study examines the role of ERK1/2 and GPR40/FFAR1 in palmitate-induced stimulation of insulin secretion and beta cell death. Methods: Insulin secretion of INS-1E cells was measured by radioimmunoassay. Protein phosphorylation was examined on Western blots. Apoptosis was assessed by TUNEL staining. Results: Palmitate and the GPR40/FFAR1 agonist TUG-469 increased phosphorylation of ERK1/2 at low (2.8 mmol/L) and high (12 mmol/L) glucose but stimulated insulin secretion only at high glucose. The MEK1 inhibitor PD98059 significantly reduced phosphorylation of ERK1/2 but did not reverse the stimulation of secretion induced by glucose, palmitate or TUG-469. PD98059 rather augmented glucose-induced secretion. Prolonged exposure to palmitate stimulated apoptosis, an effect counteracted by TUG-469. PD98059 accentuated palmitate-induced apoptosis and reversed TUG-469-mediated inhibition of cell death. Conclusions: Activation of ERK1/2 by palmitate and GPR40/FFAR1 agonist correlates neither with stimulation of insulin secretion nor with induction of apoptosis. The results suggest a significant anti-apoptotic role of ERK1/2 under conditions of lipotoxicity.

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

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

1253-P: Markers of Beta-Cell Death and Insulin Secretion in Ketosis-Prone Diabetes (KPDM)

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1253-P
Author(s):  
PRIYATHAMA VELLANKI ◽  
OMOLADE OLADEJO ◽  
MAYA FAYFMAN ◽  
GEORGIA DAVIS ◽  
ALEXANDRA MIGDAL ◽  
...  
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Death

Role of NumbL:Mig6 Interactions in Beta-Cell Death during Glucolipotoxicity

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2115-P
Author(s):  
HALESHA D. BASAVARAJAPPA ◽  
JOSE M. IRIMIA-DOMINGUEZ ◽  
PATRICK T. FUEGER
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Beta Cell Death

Role of pancreatic beta-cells in the process of beta-cell death

Diabetes ◽  
2001 ◽  
Vol 50 (Supplement 1) ◽  
pp. S52-S57 ◽  
Author(s):  
D. Pipeleers ◽  
A. Hoorens ◽  
M. Marchial-Pipeleers ◽  
M. Van de Casteele ◽  
L. Bouwens ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Beta Cell Death

scholarly journals Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma

2020 ◽  
Author(s):  
Qiuyun Yuan ◽  
Wanchun Yang ◽  
Shunxin Zhang ◽  
Tengfei Li ◽  
Mingrong Zuo ◽  
...  
Keyword(s):  
Cell Death ◽  
Malignant Glioma ◽  
Aerobic Glycolysis ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Mitochondrial Outer Membrane ◽  
Western Blots ◽  
Mitochondrial Functions ◽  
Mitochondrial Oxidative Damage

Abstract Background: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. Methods: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. Results: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown increased mitochondrial oxidative damage and decreased pro-survival AKT signaling. Conclusion: Our work identifies the oncogenic role of MTCH2 in gliomas, and establishes the causal relationship between MTCH2 expression and glioma malignancy, which may provide a potential target for future interventions.

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.

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