Stress hypERactivation in the β-cell

Fonseca, Sonya G.; Urano, Fumihiko; Burcin, Mark; Gromada, Jesper

doi:10.4161/isl.2.1.10456

Cited by 46 publications

(33 citation statements)

References 114 publications

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“…These cells are more susceptible to endoplasmic reticulum stress because of their high secreting activities and low antioxidant capacities [32] , which is in agreement to our findings. However, others reported that patulin had hyperglycemic effect due to increased glycogen phosphorylase, glucose 6-phosphatase and fructose 1, 6 diphosphatase activities as well as decreased glycolytic enzymes as hexokinase and aldolase [33] .…”

Section: Discussionsupporting

confidence: 92%

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Soliman

2017

Egyptian Journal of Histology

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Introduction: Patulin is considered the most common mycotoxins in moldy fruits especially apples and its products like juice and compote. Goji berry (lycium barbarum fruit) is a traditional Chinese herb. It has several biological activities as antioxidant, anti-aging and hypoglycemic properties. Aim: To demonstrate the toxic effect of patulin on the pancreatic tissue and to evaluate the possible role of goji extract. Material and Methods: Forty adult male albino rats were divided equally into four groups. Group I served as the control group. Group II received subcutaneous injection of 2 ml/kg/day goji extract for four weeks. Group III received subcutaneous injection of patulin 0.2 mg/kg/day for four weeks. Group IV received patulin and goji extract with the same previous doses for four weeks. Histological and immunohistochemical studies were done. Results: The administration of patulin led to degenerative changes in the pancreas. There was a significant increase in caspase-3 positive cells in both acini and islets of Langerhans. Ultrastructural examination revealed heterochromatic nuclei, cytoplasmic vacuoles and few secretory granules in acinar cells. The β cells of the islets exhibited a significant decrease in the area percentage and intensity of insulin positive cells. Goji extract could effectively improve these histological changes. Conclusion: Patulin toxicity affected both exocrine acini and β cells of islets of Langerhans. The goji extract had a protective role on this toxicity.

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Section: Discussionsupporting

confidence: 92%

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Soliman

2017

Egyptian Journal of Histology

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“…One of the events inducing differences in PTM in b-cells is disruption of homeostasis of the endoplasmic reticulum (ER) in b-cells leads to cell death and contributes to T1D pathogenesis (30)(31)(32). Upon ER stress, proteins are misfolded or modified, changing the structure of the protein.…”

Section: Discussionmentioning

confidence: 99%

Posttranslational Modification of HLA-DQ Binding Islet Autoantigens in Type 1 Diabetes

et al. 2013

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Posttranslational modification (PTM) of islet autoantigens can cause lack of central tolerance in type 1 diabetes (T1D). Tissue transglutaminase (tTG), involved in PTM of gluten antigens in celiac disease, creates negatively charged peptides favored by T1D-predisposing HLA-DQ molecules, offering an attractive candidate modifying islet autoantigens in T1D. The highly predisposing HLA-DQ8cis/trans molecules share preferences for negatively charged peptides, as well as distinct peptide-binding characteristics that distinguish their peptide-binding repertoire. We screened islet autoantigens with the tTG substrate motif for candidate-modified epitopes binding to HLA-DQ8cis/trans and identified 31 candidate islet epitopes. Deamidation was confirmed for 28 peptides (90%). Two of these epitopes preferentially bound to HLA-DQ8cis and six to HLA-DQ8trans upon deamidation, whereas all other peptides bound equally to HLA-DQ8cis/trans. HLA-DQ8cis-restricted T cells from a new-onset T1D patient could only be generated against a deamidated proinsulin peptide, but cross-reacted with native proinsulin peptide upon restimulation. The rate of T-cell autoreactivity in recent-onset T1D patients extended from 42% to native insulin to 68% adding responses to modified proinsulin, versus 20% and 37% respectively, in healthy donors. Most patients responded by interferon-g, whereas most healthy donors produced interleukin-10 only. Thus, T-cell autoreactivity exists to modified islet epitopes that differs in quality and quantity between patients and healthy donors.

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“…Role of Cdc37-Hsp90-mediated IRE1 Regulation in Insulin Production and Secretion-Insulin synthesis in pancreatic ␤-cells requires a balanced ER stress response to maintain ER flux (19,20). An increase in IRE1␣ activity is associated with insulin biosynthesis, whereas sustained IRE1␣ activity or Advmediated expression of XBP1s decreased insulin expression in ␤-cells (21,22).…”

Section: Cdc37 Regulates Ire1␣ Activity Through Direct Interaction Wimentioning

confidence: 99%

Cdc37/Hsp90 Protein-mediated Regulation of IRE1α Protein Activity in Endoplasmic Reticulum Stress Response and Insulin Synthesis in INS-1 Cells

Ota

Wang

2012

Journal of Biological Chemistry

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Background: IRE1␣ regulation in ER stress response and protein homeostasis need to be fully studied. Results: IRE1␣ binds the Cdc37-Hsp90 complex. Interfering this interaction enhanced basal IRE1␣ activity and impaired insulin synthesis in INS-1 cells. Conclusion: Negative regulation of IRE1␣ activity by Hsp90/Cdc37 is important for insulin synthesis. Significance: Hsp90/Cdc37-mediated regulation of IRE1␣ adds new mechanistic insight to ER stress signal and regulation.

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Stress hypERactivation in the β-cell

Cited by 46 publications

References 114 publications

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

Posttranslational Modification of HLA-DQ Binding Islet Autoantigens in Type 1 Diabetes

Cdc37/Hsp90 Protein-mediated Regulation of IRE1α Protein Activity in Endoplasmic Reticulum Stress Response and Insulin Synthesis in INS-1 Cells

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