scholarly journals Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact onβ-Cell Functionality

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Antonia Diaz-Ganete ◽  
Gloria Baena-Nieto ◽  
Isabel M. Lomas-Romero ◽  
Jose Francisco Lopez-Acosta ◽  
Irene Cozar-Castellano ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Insulin Secretion ◽  
Endoplasmic Reticulum Stress ◽  
Cell Mass ◽  
Slowing Down ◽  
Stress Markers ◽  
Murine Cell Line ◽  
Survival Pathways

Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment forβ-cells known as insulitis, which results in loss ofβ-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserveβ-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFαand/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects onβ-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis onβ-cells.

Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes

Diabetologia ◽  
2012 ◽  
Vol 55 (9) ◽  
pp. 2417-2420 ◽  
Author(s):  
I. Marhfour ◽  
X. M. Lopez ◽  
D. Lefkaditis ◽  
I. Salmon ◽  
F. Allagnat ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Endoplasmic Reticulum Stress ◽  
Stress Markers

scholarly journals Genetic Predisposition for Type 1 Diabetes Mellitus - The Role of Endoplasmic Reticulum Stress in Human Disease Etiopathogenesis

2010 ◽  
Vol 29 (3) ◽  
pp. 139-149 ◽  
Author(s):  
Karmen Stankov
Keyword(s):  
Diabetes Mellitus ◽  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Endoplasmic Reticulum Stress ◽  
Type 1 Diabetes Mellitus ◽  
Genetic Predisposition ◽  
Human Disease ◽  
Wolfram Syndrome

Genetic Predisposition for Type 1 Diabetes Mellitus - The Role of Endoplasmic Reticulum Stress in Human Disease EtiopathogenesisThe increasing incidence of diabetes mellitus worldwide has prompted a rapid growth in the pace of scientific discovery of the mechanisms involved in the etiopathogenesis of this multifactorial disease. Accumulating evidence suggests that endoplasmic reticulum stress plays a role in the pathogenesis of diabetes, contributing to pancreatic beta cell loss and insulin resistance. Wolfram syndrome is an autosomal recessive neurodegenerative disorder accompanied by insulin-dependent diabetes mellitus and progressive optic atrophy. The pathogenesis of this rare neurodegenerative genetic disease is unknown. A Wolfram gene (WFS1 locus) has recently been mapped to chromosome 4p16.1, but there is evidence for locus heterogeneity, including the mitochondrial genome deletion. Recent positional cloning led to identification of the second WFS locus, a mutation in the CISD2 gene, which encodes an endoplasmic reticulum intermembrane small protein. Our results were obtained by the analysis of a families belonging to specific population, affected by Wolfram syndrome. We have identified the newly diagnosed genetic alteration of WFS1 locus, a double non-synonymous and frameshift mutation, providing further evidence for the genetic heterogeneity of this syndrome. Newly identified mutations may contribute to the further elucidation of the pathogenesis of Wolfram syndrome, as well as of the complex mechanisms involved in diabetes mellitus development.

scholarly journals Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

2021 ◽  
Vol 22 (9) ◽  
pp. 4646
Author(s):  
Alexey A. Tinkov ◽  
Monica M. B. Paoliello ◽  
Aksana N. Mazilina ◽  
Anatoly V. Skalny ◽  
Airton C. Martins ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Synaptic Dysfunction ◽  
Future Research ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Future Research Directions ◽  
The Impact

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

2021 ◽  
Author(s):  
Ankita Bhardwaj ◽  
Rishi Bhardwaj ◽  
Shweta Sharma ◽  
Suresh Kumar Sharma ◽  
Devinder Kumar Dhawan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cognitive Impairment ◽  
Endoplasmic Reticulum Stress

scholarly journals Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2

2006 ◽  
Vol 26 (12) ◽  
pp. 4553-4563 ◽  
Author(s):  
Seon-Yong Yeom ◽  
Geun Hyang Kim ◽  
Chan Hee Kim ◽  
Heun Don Jung ◽  
So-Yeon Kim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Endocrine Cells ◽  
Potential Role ◽  
Cell Mass ◽  
Dominant Negative ◽  
Transcriptional Coactivator ◽  
Β Cells ◽  
Β Cell ◽  
Islet Mass

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

The Role of Endoplasmic Reticulum Stress and NLRP3 Inflammasomes in the Development of Atherosclerosis

2021 ◽  
Vol 55 (4) ◽  
pp. 331-339
Author(s):  
V. V. Pushkarev ◽  
L. K. Sokolova ◽  
O. I. Kovzun ◽  
V. M. Pushkarev ◽  
M. D. Tronko
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Nlrp3 Inflammasomes
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