scholarly journals Activation of Nicotinic Acetylcholine Receptors Decreases Apoptosis in Human and Female Murine Pancreatic Islets

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 3800-3808 ◽  
Author(s):  
Philippe Klee ◽  
Domenico Bosco ◽  
Audrey Guérardel ◽  
Emmanuel Somm ◽  
Audrey Toulotte ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
B Cell Lymphoma ◽  
Β Cells ◽  
Β Cell ◽  
Nicotinic Acetylcholine ◽  
Mitochondrial Outer Membrane Permeabilization

Type 1 diabetes (T1DM) results from destruction of most insulin-secreting pancreatic β-cells. The persistence of β-cells decades after the onset of the disease indicates that the resistance of individual cells to the autoimmune insult is heterogeneous and might depend on the metabolic status of a cell at a given moment. The aim of this study is to investigate whether activation of nicotinic acetylcholine receptors (nACh-Rs) could increase β-cell resistance against the adverse environment prevailing at the onset of T1DM. Here, we show that nACh-R activation by nicotine and choline, 2 agonists of the receptor, decreases murine and human β-cell apoptosis induced by proinflammatory cytokines known to be present in the islet environment at the onset of T1DM. The protective mechanism activated by nicotine and choline involves attenuation of mitochondrial outer membrane permeabilization via modulation of endoplasmic reticulum stress, of the activity of B-cell lymphoma 2 family proteins and cytoplasmic calcium levels. Local inflammation and endoplasmic reticulum stress being key determinants of β-cell death in T1DM, we conclude that pharmacological activation of nACh-R could represent a valuable therapeutic option in the modulation of β-cell death in T1DM.

Estrogen reduces endoplasmic reticulum stress to protect against glucotoxicity induced-pancreatic β-cell death

2014 ◽  
Vol 139 ◽  
pp. 25-32 ◽  
Author(s):  
Suwattanee Kooptiwut ◽  
Pitchnischa Mahawong ◽  
Wanthanee Hanchang ◽  
Namoiy Semprasert ◽  
Suchada Kaewin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Protection of pancreatic β-cells by exendin-4 may involve the reduction of endoplasmic reticulum stress; in vivo and in vitro studies

2007 ◽  
Vol 193 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Shin Tsunekawa ◽  
Naoki Yamamoto ◽  
Katsura Tsukamoto ◽  
Yuji Itoh ◽  
Yukiko Kaneko ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Islet Cells ◽  
Binding Protein ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

The aim of this study was to investigate the in vivo and in vitro effects of exendin-4, a potent glucagon-like peptide 1 agonist, on the protection of the pancreatic β-cells against their cell death. In in vivo experiments, we used β-cell-specific calmodulin-overexpressing mice where massive apoptosis takes place in their β-cells, and we examined the effects of chronic treatment with exendin-4. Chronic and s.c. administration of exendin-4 reduced hyperglycemia. The treatment caused significant increases of the insulin contents of the pancreas and islets, and retained the insulin-positive area. Dispersed transgenic islet cells lived only shortly, and several endoplasmic reticulum (ER) stress-related molecules such as immunoglobulin-binding protein (Bip), inositol-requiring enzyme-1α, X-box-binding protein-1 (XBP-1), RNA-activated protein kinase-like endoplasmic reticulum kinase, activating transcription factor-4, and C/EBP-homologous protein (CHOP) were more expressed in the transgenic islets. We also found that the spliced form of XBP-1, a marker of ER stress, was also increased in β-cell-specific calmodulin-overexpressing transgenic islets. In the quantitative real-time PCR analyses, the expression levels of Bip and CHOP were reduced in the islets from the transgenic mice treated with exendin-4. These findings suggest that excess of ER stress occurs in the transgenic β-cells, and the suppression of ER stress and resultant protection against cell death may be involved in the anti-diabetic effects of exendin-4.

Role of nicotinic acetylcholine receptors in the regulation of kainic acid-induced hippocampal cell death in mice

2004 ◽  
Vol 64 (4) ◽  
pp. 309-317 ◽  
Author(s):  
Han-Kyu Lee ◽  
Seong-Soo Choi ◽  
Eun-Jung Han ◽  
Jin-Young Lee ◽  
Min-Soo Kwon ◽  
...  
Keyword(s):  
Cell Death ◽  
Kainic Acid ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Hippocampal Cell

scholarly journals Autophagy plays a protective role in endoplasmic reticulum stress-mediated pancreatic β cell death

Autophagy ◽  
2012 ◽  
Vol 8 (12) ◽  
pp. 1757-1768 ◽  
Author(s):  
Alberto Bartolome ◽  
Carlos Guillen ◽  
Manuel Benito
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Protective Role ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Lactogens reduce endoplasmic reticulum stress-induced rodent and human β-cell death and diabetes incidence in Akita mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Rosemary Li ◽  
Nagesha Guthalu Kondegowda ◽  
Joanna Filipowska ◽  
Rollie F. Hampton ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Placental Lactogen ◽  
Diabetes Incidence ◽  
Β Cells ◽  
Β Cell ◽  
Akita Mice ◽  
Stress Pathway

Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent and human β-cells <i>in vitro</i> and<i> in vivo</i> against triggers of β-cell cytotoxicity relevant to diabetes, many of which converge onto a common pathway, endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines if lactogens can protect β-cells against ER stress and mitigate diabetes incidence in Akita mice, a rodent model of ER stress-induced diabetes, akin to neonatal diabetes in humans. We show that lactogens protect INS1 cells, primary rodent and human β-cells <i>in vitro</i> against two distinct ER stressors, tunicamycin and thapsigargin, through activation of the JAK2/STAT5 pathway. Lactogens mitigate expression of pro-apoptotic molecules in the ER stress pathway that are induced by chronic ER stress in INS1 cells and rodent islets. Transgenic expression of placental lactogen in β-cells of Akita mice drastically reduces the severe hyperglycemia, diabetes incidence, hypoinsulinemia, β-cell death, and loss of β-cell mass observed in Akita littermates. These are the first studies in any cell type demonstrating lactogens modulate the ER stress pathway, causing enhanced β-cell survival and reduced diabetes incidence in the face of chronic ER stress.

Stress-Associated Endoplasmic Reticulum Protein 1 Protected High Glucose-Induced Islet β Cells from Apoptosis by Attenuating Endoplasmic Reticulum Stress

2019 ◽  
Vol 9 (12) ◽  
pp. 1731-1738
Author(s):  
Shulong Guo ◽  
Shaoya Wang ◽  
Youxiao Zeng ◽  
Qiaosheng Hu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Western Blotting ◽  
High Glucose ◽  
Islet Cell ◽  
Β Cells ◽  
Β Cell ◽  
Tnf Α ◽  
Endoplasmic Reticulum Protein ◽  
Related Proteins

The incidence of type II diabetes caused by islet cell injury is increasing in recent years. Endoplasmic reticulum stress is one of the crucial causes of islet β cell damage, and stress-associated endoplasmic reticulum protein 1 (SERP1) could inhibit the occurrence and development of endoplasmic reticulum stress. But whether SERP1 could inhibit the damage of islet β cell caused by endoplasmic reticulum stress is unclear. In this study, we detected the levels of SERP1 and endoplasmic reticulum stress related proteins (p-PERK, p-Eif2 α, ATF-4 and CHOP) by western blotting. Next the lentivirus was used to construct the islet cell line which was stable overexpressed SERP1. Then the expression of endoplasmic reticulum stress related proteins and inflammatory factors was determined with western blotting. At last the apoptosis rates of islet β cells were detected by flow cytometry. We found that high glucose medium promoted the expression of p-PERK, p-Eif2 α, ATF-4 and CHOP while downregulated the levels of SERP1 in isletβ cells. Moreover, overexpression of SERP1 induced the downregulation of levels of p-PERK, p-Eif2 α, ATF-4, CHOP, TNF-α , IL-1β and IL-6 and alleviated the apoptosis of islet cells. At last, the overexpression of CHOP rescued the apoptosis rates and the expression of TNF-α, IL-1β and IL-6. These results indicated SERP1 relieved the inflammation response and apoptosis of islet β cells by inhibiting the expression of CHOP and alleviating the endoplasmic reticulum stress induced damage.

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