GDF15 Is Induced by T1D-Associated Cytokines and ER Stress and Promotes Beta-Cell Apoptosis

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2109-P ◽  
Author(s):  
GUANLAN XU ◽  
LANCE THIELEN ◽  
JUNQIN CHEN ◽  
SEONGHO JO ◽  
ANATH SHALEV
Keyword(s):  
Beta Cell ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Beta Cell Apoptosis

ER Stress Induces Beta-Cell Apoptosis

2008 ◽  
Vol 8 (7) ◽  
pp. 29-30
Author(s):  
N. Canavan ◽  
D. L. Eizirik
Keyword(s):  
Beta Cell ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Beta Cell Apoptosis

scholarly journals The miRNAs miR-211-5p and miR-204-5p modulate ER stress in human beta cells

2019 ◽  
Vol 63 (2) ◽  
pp. 139-149 ◽  
Author(s):  
Fabio Arturo Grieco ◽  
Andrea Alex Schiavo ◽  
Flora Brozzi ◽  
Jonas Juan-Mateu ◽  
Marco Bugliani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Er Stress ◽  
Beta Cells ◽  
Cell Apoptosis ◽  
Interleukin 1 ◽  
Pancreatic Beta Cell ◽  
Beta Cell Apoptosis ◽  
Human Beta Cells

miRNAs are a class of small non-coding RNAs that regulate gene expression. Type 1 diabetes is an autoimmune disease characterized by insulitis (islets inflammation) and pancreatic beta cell destruction. The pro-inflammatory cytokines interleukin 1 beta (IL1B) and interferon gamma (IFNG) are released during insulitis and trigger endoplasmic reticulum (ER) stress and expression of pro-apoptotic members of the BCL2 protein family in beta cells, thus contributing to their death. The nature of miRNAs that regulate ER stress and beta cell apoptosis remains to be elucidated. We have performed a global miRNA expression profile on cytokine-treated human islets and observed a marked downregulation of miR-211-5p. By real-time PCR and Western blot analysis, we confirmed cytokine-induced changes in the expression of miR-211-5p and the closely related miR-204-5p and downstream ER stress related genes in human beta cells. Blocking of endogenous miRNA-211-5p and miR-204-5p by the same inhibitor (it is not possible to block separately these two miRs) increased human beta cell apoptosis, as measured by Hoechst/propidium Iodide staining and by determination of cleaved caspase-3 activation. Interestingly, miRs-211-5p and 204-5p regulate the expression of several ER stress markers downstream of PERK, particularly the pro-apoptotic protein DDIT3 (also known as CHOP). Blocking CHOP expression by a specific siRNA partially prevented the increased apoptosis observed following miR-211-5p/miR-204-5p inhibition. These observations identify a novel crosstalk between miRNAs, ER stress and beta cell apoptosis in early type 1 diabetes.

Ruthenium complexes as inhibitors of human islet amyloid polypeptide aggregation, an effect that prevents beta cell apoptosis

RSC Advances ◽  
2015 ◽  
Vol 5 (23) ◽  
pp. 17405-17412 ◽  
Author(s):  
Lijuan Ma ◽  
Yuanting Fu ◽  
Lianling Yu ◽  
Xiaoling Li ◽  
Wenjie Zheng ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Apoptosis ◽  
Cell Damage ◽  
Islet Amyloid Polypeptide ◽  
Ruthenium Complexes ◽  
Human Islet ◽  
Ros Generation ◽  
Beta Cell Apoptosis ◽  
Islet Amyloid ◽  
Application Potential

Herein we show that ruthenium complexes could inhibit fibrosis of hIAPP and protect the hIAPP-induced cell damage by suppressing ROS generation, indicating the application potential of the complexes in treatment of T2DM by targeting hIAPP.

Imidazoline compounds protect against interleukin 1beta-induced beta-cell apoptosis

Diabetes ◽  
2001 ◽  
Vol 50 (Supplement 1) ◽  
pp. S70-S76 ◽  
Author(s):  
S. V. Zaitsev ◽  
I. B. Appelskog ◽  
I. L. Kapelioukh ◽  
S. Yang ◽  
M. K hler ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Apoptosis ◽  
Beta Cell Apoptosis ◽  
Interleukin 1Beta ◽  
Imidazoline Compounds

scholarly journals Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis

Diabetologia ◽  
2009 ◽  
Vol 52 (4) ◽  
pp. 626-635 ◽  
Author(s):  
S. Zraika ◽  
R. L. Hull ◽  
J. Udayasankar ◽  
K. Aston-Mourney ◽  
S. L. Subramanian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Cell Apoptosis ◽  
Beta Cell Apoptosis ◽  
Amyloid Formation ◽  
Islet Amyloid

scholarly journals Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0241349
Author(s):  
Sajid Ali Rajput ◽  
Munazza Raza Mirza ◽  
M. Iqbal Choudhary
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Proinflammatory Cytokines ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Beta Cell Apoptosis ◽  
Atp Levels ◽  
Induced Apoptosis

Beta cell apoptosis induced by proinflammatory cytokines is one of the hallmarks of diabetes. Small molecules which can inhibit the cytokine-induced apoptosis could lead to new drug candidates that can be used in combination with existing therapeutic interventions against diabetes. The current study evaluated several effects of bergenin, an isocoumarin derivative, in beta cells in the presence of cytokines. These included (i) increase in beta cell viability (by measuring cellular ATP levels) (ii) suppression of beta cell apoptosis (by measuring caspase activity), (iii) improvement in beta cell function (by measuring glucose-stimulated insulin secretion), and (iv) improvement of beta cells mitochondrial physiological functions. The experiments were carried out using rat beta INS-1E cell line in the presence or absence of bergenin and a cocktail of proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, and interferon- gamma) for 48 hr. Bergenin significantly inhibited beta cell apoptosis, as inferred from the reduction in the caspase-3 activity (IC50 = 7.29 ± 2.45 μM), and concurrently increased cellular ATP Levels (EC50 = 1.97 ± 0.47 μM). Bergenin also significantly enhanced insulin secretion (EC50 = 6.73 ± 2.15 μM) in INS-1E cells, presumably because of the decreased nitric oxide production (IC50 = 6.82 ± 2.83 μM). Bergenin restored mitochondrial membrane potential (EC50 = 2.27 ± 0.83 μM), decreased ROS production (IC50 = 14.63 ± 3.18 μM), and improved mitochondrial dehydrogenase activity (EC50 = 1.39 ± 0.62 μM). This study shows for the first time that bergenin protected beta cells from cytokine-induced apoptosis and restored insulin secretory function by virtue of its anti-inflammatory, antioxidant and anti-apoptotic properties. To sum up, the above mentioned data highlight bergenin as a promising anti-apoptotic agent in the context of diabetes.

scholarly journals MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes

2014 ◽  
Vol 20 (4) ◽  
pp. 385-397 ◽  
Author(s):  
Amin Ardestani ◽  
Federico Paroni ◽  
Zahra Azizi ◽  
Supreet Kaur ◽  
Vrushali Khobragade ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Apoptosis ◽  
Beta Cell Apoptosis
Sign in / Sign up

Export Citation Format

Share Document