Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells

Raciti, Gregory Alexander; Iadicicco, Claudia; Ulianich, Luca; Vind, Birgitte F.; Gaster, Michael; Andreozzi, Francesco; Longo, Michele; Teperino, Raffaele; Ungaro, Paola; Jeso, Bruno Di; Formisano, Pietro; Béguinot, Francesco; Miele, Claudia

doi:10.1007/s00125-010-1676-1

Cited by 56 publications

(52 citation statements)

References 49 publications

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“…Elevated levels of ER stress have been observed in animal models of hyperglycemia, obesity, and dyslipidemia ( 6,7,30,37,38 ). In a hyperglycemic state, GLN, a metabolite of glucose, accumulates within cells and acts as a potent inducer of ER stress (39)(40)(41). In addition, lipids such as PA and unesterifi ed cholesterol are thought to disturb ER function by disrupting the composition of the ER membrane ( 11,42 ).…”

Section: Discussionmentioning

confidence: 99%

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

McAlpine

Werstuck²

2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org cause of cerebrovascular and cardiovascular diseases, which together account for a third of all deaths in Western societies ( 1, 2 ). Multiple risk factors contribute to the initiation and progression of atherosclerosis including diabetes mellitus, hypertension, obesity, dyslipidemia, a sedentary life style, and smoking ( 3 ). One of the hallmark features of every stage of atherogenesis, from the fatty streak to the complex plaque, is the presence of lipid-laden macrophages known as foam cells. Intimal macrophage/foam cells accumulate lipids from LDL and modifi ed LDL particles and secrete a variety of infl ammatory cytokines. In advanced plaques, foam cells undergo apoptosis, thereby contributing to the formation of a highly thrombotic, lipid rich, necrotic core [reviewed by Moore and Tabas ( 4 )]. The molecular events that promote the initiation and development of atherosclerosis are poorly understood. A better understanding of the signaling networks that regulate foam cell formation and atherosclerotic plaque development may lead to the identifi cation of novel therapeutic targets.The endoplasmic reticulum (ER) is the organelle responsible for the proper folding, modifi cation, and processing of secretory, transmembrane, and ER resident proteins. If the processing capacity of the ER is overwhelmed, unfolded or misfolded proteins begin to accumulate, a condition known as ER stress. The accumulation of misfolded proteins triggers the initiation of the unfolded protein response (UPR), which is composed of three signaling cascades regulated by ER transmembrane Atherosclerosis is an infl ammatory disease within the walls of medium and large arteries ( 1 ). It is the leading C. S.

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Section: Discussionmentioning

confidence: 99%

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

McAlpine

Werstuck²

2014

Journal of Lipid Research

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“…Under physiological conditions, only 1-3% of intracellular glucose enters the hexosamine pathway; however, the flux increases with glucose concentration [9]. Increased HBP flux, in turn, causes hyper-O-GlcNAc of proteins [10], oxidative stress [11] and ER stress, although this last mechanism has been demonstrated in cells other than beta cells [12,29].…”

Section: Discussionmentioning

confidence: 99%

Increased hexosamine biosynthetic pathway flux dedifferentiates INS-1E cells and murine islets by an extracellular signal-regulated kinase (ERK)1/2-mediated signal transmission pathway

et al. 2011

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Aims/hypothesis Beta cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (decline of glucose-stimulated insulin secretion, downregulation of specific gene expression). Apoptosis and dysfunction are caused, at least in part, by lipoglucotoxicity. The mechanisms implicated are oxidative stress, increase in the hexosamine biosynthetic pathway (HBP) flux and endoplasmic reticulum (ER) stress. Oxidative stress plays a role in glucotoxicity-induced beta cell dedifferentiation, while glucotoxicity-induced ER stress has been mostly linked to beta cell apoptosis. We sought to clarify whether ER stress caused by increased HBP flux participates in a dedifferentiating response of beta cells, in the absence of relevant apoptosis. Methods We used INS-1E cells and murine islets. We analysed the unfolded protein response and the expression profile of beta cells by real-time RT-PCR and western blot. The signal transmission pathway elicited by ER stress was investigated by real-time RT-PCR and immunofluorescence. Results Glucosamine and high glucose induced ER stress, but did not decrease cell viability in INS-1E cells. ER stress caused dedifferentiation of beta cells, as shown by downregulation of beta cell markers and of the transcription factor, pancreatic and duodenal homeobox 1. Glucose-stimulated insulin secretion was inhibited. These effects were prevented by the chemical chaperone, 4-phenyl butyric acid. The extracellular signal-regulated kinase (ERK) signal transmission pathway was implicated, since its inhibition prevented the effects induced by glucosamine and high glucose. Conclusions/interpretation Glucotoxic ER stress dedifferentiates beta cells, in the absence of apoptosis, through a transcriptional response. These effects are mediated by the activation of ERK1/2.

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“…Specifically, some antidiabetic and antioxidative agents, such as lipoic acid, oligomannuronate, metformin and selenium-enriched exopolysaccharides, can improve skeletal muscle glucose uptake through AMPK/PGC-1α/GLUT4 pathway (Wang et al 2010, Hao et al 2011. Consistently, both ER stress and oxidative stress are reported to impair GLUT4 production and glucose uptake via a PGC-1α-dependent signaling pathway (Raciti et al 2010, Aoi et al 2013. Moreover, aberrant DNA methylation in the PGC-1α promoter sequence also contributes to impaired glucose tolerance by influencing the expression of PGC-1α and GLUT4 in skeletal muscle (Zeng et al 2013).…”

Section: Glucose Uptakementioning

confidence: 96%

PGC-1α, glucose metabolism and type 2 diabetes mellitus

Deng

Shi

et al. 2016

Journal of Endocrinology

125

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Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by glucose metabolic disturbance. A number of transcription factors and coactivators are involved in this process. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important transcription coactivator regulating cellular energy metabolism. Accumulating evidence has indicated that PGC-1α is involved in the regulation of T2DM. Therefore, a better understanding of the roles of PGC-1α may shed light on more efficient therapeutic strategies. Here, we review the most recent progress on PGC-1α and discuss its regulatory network in major glucose metabolic tissues such as the liver, skeletal muscle, pancreas and kidney. The significant associations between PGC-1α polymorphisms and T2DM are also discussed in this review.

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Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells

Cited by 56 publications

References 49 publications

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

Increased hexosamine biosynthetic pathway flux dedifferentiates INS-1E cells and murine islets by an extracellular signal-regulated kinase (ERK)1/2-mediated signal transmission pathway

PGC-1α, glucose metabolism and type 2 diabetes mellitus

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