Nicorandil Attenuates High Glucose-Induced Insulin Resistance by Suppressing Oxidative Stress-Mediated Endoplasmic Reticulum Stress Protein Kinase RNA-Like Endoplasmic Reticulum Kinase Singling Pathway

2020 ◽  
Author(s):  
Zhongwei Liu ◽  
Haitao Zhu ◽  
Chunhui He ◽  
Ting He ◽  
Shuo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Endoplasmic Reticulum Stress ◽  
High Glucose ◽  
Stress Protein

scholarly journals Nicorandil attenuates high glucose-induced insulin resistance by suppressing oxidative stress-mediated ER stress PERK signaling pathway

2021 ◽  
Vol 9 (1) ◽  
pp. e001884
Author(s):  
Zhongwei Liu ◽  
Haitao Zhu ◽  
Chunhui He ◽  
Ting He ◽  
Shuo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Er Stress ◽  
High Glucose ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

IntroductionGlucose-induced insulin resistance is a typical character of diabetes. Nicorandil is now widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress, which are involved in insulin resistance. Here, we investigated mechanisms of nicorandil’s novel pharmacological activity on insulin resistance in diabetes.Research design and methodsNicorandil was administrated to streptozotocin-induced animals with diabetes and high glucose exposed skeletal muscle cells. Insulin resistance and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress signaling activation and glucose uptake were assessed.ResultsNicorandil attenuated high glucose-induced insulin resistance without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in rats with diabetes. Nicorandil treatment suppressed protein kinase C/nicotinamide adenine dinucleotide phosphate oxidases system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress-mediated ER stress protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α/activating transcription factor 4/CEBP homologous protein/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil downregulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells.ConclusionsBy reducing cytoplasmic calcium, nicorandil alleviated high glucose-induced insulin resistance by inhibiting oxidative stress-mediated ER stress PERK pathway.

Fish oil supplementation inhibits endoplasmic reticulum stress and improves insulin resistance: involvement of AMP-activated protein kinase

2017 ◽  
Vol 8 (4) ◽  
pp. 1481-1493 ◽  
Author(s):  
Wenqi Yang ◽  
Xu Chen ◽  
Ming Chen ◽  
Yanping Li ◽  
Qing Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Endoplasmic Reticulum Stress ◽  
Fish Oil ◽  
Er Stress ◽  
Protective Effects ◽  
Ampk Activation ◽  
Amp Activated Protein Kinase ◽  
Fish Oil Supplementation

ER stress inhibition through AMPK activation may explain the protective effects of fish oil against HFD-induced insulin resistance.

scholarly journals Moderate Exercise Prevents Functional Remodeling of the Anterior Pituitary Gland in Diet-Induced Insulin Resistance in Rats: Role of Oxidative Stress and Autophagy

Endocrinology ◽  
2015 ◽  
Vol 157 (3) ◽  
pp. 1135-1145 ◽  
Author(s):  
María E. Mercau ◽  
Esteban M. Repetto ◽  
Matías N. Perez ◽  
Camila Martinez Calejman ◽  
Silvia Sanchez Puch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Antioxidant Enzymes ◽  
Endoplasmic Reticulum Stress ◽  
Palmitic Acid ◽  
Pituitary Gland ◽  
Moderate Exercise ◽  
Glucocorticoid Production

Abstract A sustained elevation of glucocorticoid production, associated with the establishment of insulin resistance (IR) could add to the deleterious effects of the IR state. The aim of this study is to analyze the consequences of long-term feeding with a sucrose-rich diet (SRD) on Pomc/ACTH production, define the underlying cellular processes, and determine the effects of moderate exercise (ME) on these parameters. Animals fed a standard chow with or without 30% sucrose in the drinking water were subjected to ME. Circulating hormone levels were determined, and pituitary tissues were processed and analyzed by immunobloting and quantitative real-time PCR. Parameters of oxidative stress (OxS), endoplasmic reticulum stress, and autophagy were also determined. Rats fed SRD developed a decrease in pituitary Pomc/ACTH expression levels, increased expression of antioxidant enzymes, and induction of endoplasmic reticulum stress and autophagy. ME prevented pituitary dysfunction as well as induction of antioxidant enzymes and autophagy. Reporter assays were performed in AtT-20 corticotroph cells incubated in the presence of palmitic acid. Pomc transcription was inhibited by palmitic acid-dependent induction of OxS and autophagy, as judged by the effect of activators and inhibitors of both processes. Long-term feeding with SRD triggers the generation of OxS and autophagy in the pituitary gland, which could lead to a decline in Pomc/ACTH/glucocorticoid production. These effects could be attributed to an increase in fatty acids availability to the pituitary gland. ME was able to prevent these alterations, suggesting additional beneficial effects of ME as a therapeutic strategy in the management of IR.

scholarly journals Oxidative Stress-Induced Diseases via the ASK1 Signaling Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Mayumi Soga ◽  
Atsushi Matsuzawa ◽  
Hidenori Ichijo
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Mechanisms ◽  
Cellular Functions ◽  
Mapk Kinase ◽  
Mitogen Activated Protein

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase that activates the downstream MAPKs, c-Jun N-terminal kinase (JNK) and p38. ASK1 is activated by various types of stress, such as oxidative stress, endoplasmic reticulum stress, and infection, and regulates various cellular functions. Recently, it has been reported that ASK1 is associated with various diseases induced by oxidative stress. In this review, we introduce recent findings of the regulatory mechanisms of ASK1 and the oxidative stress-induced diseases mediated by the ASK1 signaling pathway.

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