Endoplasmic reticulum stress in insulin resistance and diabetes

Guerrero‐Hernández, Agustín; León-Aparicio, Daniel; Chávez-Reyes, Jesús; Olivares-Reyes, J. Alberto; DeJesus, Silvia

doi:10.1016/j.ceca.2014.08.006

Cited by 58 publications

(39 citation statements)

References 183 publications

(265 reference statements)

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“…This directly influences the function of the ER, affecting its roles in protein and sterol synthesis, lipid metabolism, and signal transduction (Coe and Michalak, 2009; Krebs et al, 2015). Inhibition of SERCA causes depletion of ER Ca 2+ stores and disruption of ER Ca 2+ homeostasis, leading to induction of ER stress and the UPR to control damage and re-establish ER homeostasis (Guerrero-Hernandez et al, 2014). …”

Section: Obesity and Aberrant Activation Of The Upr In The Ovarymentioning

confidence: 99%

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Qiao

2016

Protein &Amp; Cell

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The endoplasmic reticulum (ER) is the principal organelle responsible for several specific cellular functions including synthesis and folding of secretory or membrane proteins, lipid metabolism, and Ca2+ storage. Different physiological as well as pathological stress conditions can, however, perturb ER homeostasis, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition termed ER stress. To deal with an increased folding demand, cells activate the unfolded protein response (UPR), which is initially protective but can become detrimental if ER stress is severe and prolonged. Accumulating evidence demonstrates a link between the UPR and ovarian development and function, including follicular growth and maturation, follicular atresia, and corpus luteum biogenesis. Additionally, ER stress and the UPR may also play an important role in the ovary under pathological conditions. Understanding the molecular mechanisms related to the dual role of unfolded protein response in the ovarian physiology and pathology may reveal the pathogenesis of some reproductive endocrine diseases and provide a new guidance to improve the assisted reproductive technology. Here we review the current literature and discuss concepts and progress in understanding the UPR, and we also analyze the role of ER stress and the UPR in the ovary.

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Section: Obesity and Aberrant Activation Of The Upr In The Ovarymentioning

confidence: 99%

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Qiao

2016

Protein &Amp; Cell

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“…El RE desempeña un papel determinante en la homeostasis del Ca 2+ y participa en la maduración y la expresión de proteí-nas de membrana y de secreción. En condiciones de estrés celular que incrementan la demanda del RE y que conllevan una sobrecarga de su capacidad funcional se genera una serie de alteraciones conocidas como «estrés del retículo», que incluyen la disminución del transporte de proteínas hacia el aparato de Golgi, la expresión de proteínas mal plegadas y la depleción del calcio de este reservorio 50 . Bajo estas condiciones, el RE activa un mecanismo compensatorio denominado «respuesta de proteínas mal plegadas» (UPR, unfolding protein response), que intenta restablecer la homeostasis de las funciones del RE 50 .…”

Section: Papel De Los áCidos Grasos En El Estrés Del Retículo Endopláunclassified

“…Se ha detectado que la actividad de JNK se encuentra elevada en modelos animales de obesidad 58,60 , y la deleción de las isoformas 1 y 2 de JNK protege a los ratones de la resistencia a la insulina inducida por una dieta alta en grasa 61,62 . En investigación molecular, evidencias experimentales indican que JNK fosforila por una parte a IRS-1 en la serina 307, fosforilación que se ha asociado a la disminución de las acciones de la insulina por alterar la asociación entre el receptor de insulina e IRS-1 63,64 , y por otra fosforila a IKKβ que lleva a la activación del NFκB y a la regulación de las respuestas inflamatorias 50,65 . Además de la fosforilación de IRS mediada por JNK, existen otros mecanismos asociados con la resistencia a la insulina inducida por el estrés del RE.…”

Section: Papel De Los áCidos Grasos En El Estrés Del Retículo Endopláunclassified

El papel de los ácidos grasos libres en la resistencia a la insulina

Vazquez-Jimenez¹,

Roura-Guiberna²,

Jiménez-Mena³

et al. 2017

GMM

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“…Endoplasmic reticulum (ER) stress, a common cellular stress response that is triggered by a variety of conditions that disturb cellular homeostasis, is not only associated with pancreatic β-cell dysfunction and apoptosis [12,13], but is also closely related to autophagy activation [14,15]. It is obvious that ER stress, autophagy, and apoptosis are interlocked in an extensive crosstalk [16].…”

Section: Introductionmentioning

confidence: 99%

Intermittent-Hypoxia-Induced Autophagy Activation Through the ER-Stress-Related PERK/eIF2α/ATF4 Pathway is a Protective Response to Pancreatic β-Cell Apoptosis

Song

Tan

Miao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intermittent hypoxia (IH) causes apoptosis in pancreatic β-cells, but the potential mechanisms remain unclear. Endoplasmic reticulum (ER) stress, autophagy, and apoptosis are interlocked in an extensive crosstalk. Thus, this study aimed to investigate the contributions of ER stress and autophagy to IH-induced pancreatic β-cell apoptosis. Methods: We established animal and cell models of IH, and then inhibited autophagy and ER stress by pharmacology and small interfering RNA (siRNA) in INS-1 cells and rats. The levels of biomarkers for autophagy, ER stress, and apoptosis were evaluated by immunoblotting and immunofluorescence. The number of autophagic vacuoles was observed by transmission electron microscopy. Results: IH induced autophagy activation both in vivo and in vitro, as evidenced by increased autophagic vacuole formation and LC3 turnover, and decreased SQSTM1 level. The levels of ER-stress-related proteins, including GRP78, CHOP, caspase 12, phosphorylated (p)-protein kinase RNA-like ER kinase (PERK), p-eIF2α, and activating transcription factor 4 (ATF4) were increased under IH conditions. Inhibition of ER stress with tauroursodeoxycholic acid or 4-phenylbutyrate partially blocked IH-induced autophagy in INS-1 cells. Furthermore, inhibition of PERK with GSK2606414 or siRNA blocked the ERstress-related PERK/eIF2α/ATF4 signaling pathway and inhibited autophagy induced by IH, which indicates that IH-induced autophagy activation is dependent on this signaling pathway. Promoting autophagy with rapamycin alleviated IH-induced apoptosis, whereas inhibition of autophagy with chloroquine or autophagy-related gene (Atg5 and Atg7) siRNA aggravated pancreatic β-cell apoptosis caused by IH. Conclusion: IH induces autophagy activation through the ER-stress-related PERK/eIF2α/ATF4 signaling pathway, which is a protective response to pancreatic β-cell apoptosis caused by IH.

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Endoplasmic reticulum stress in insulin resistance and diabetes

Cited by 58 publications

References 183 publications

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

Dual role for the unfolded protein response in the ovary: adaption and apoptosis

El papel de los ácidos grasos libres en la resistencia a la insulina

Intermittent-Hypoxia-Induced Autophagy Activation Through the ER-Stress-Related PERK/eIF2α/ATF4 Pathway is a Protective Response to Pancreatic β-Cell Apoptosis

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