A guide to understanding endoplasmic reticulum stress in metabolic disorders

Lemmer, Imke L.; Willemsen, Nienke; Hilal, Nazia; Bartelt, Alexander

doi:10.1016/j.molmet.2021.101169

Cited by 200 publications

(139 citation statements)

References 206 publications

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“…During ER stress, the activation of the IRE1 pathway is essential for the synthesis and maturation of insulin, but hyperactivated IRE1 results in β-cell death through the initiation of JNK and caspases cascade [ 224 , 225 ]. The PERK-EIF2α-CHOP axis acts as a switch between a correct function of pancreatic β-cell and its survival ability.…”

Section: Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Burillo

Marqués

Jiménez

et al. 2021

Cells

116

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Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

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Section: Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Burillo

Marqués

Jiménez

et al. 2021

Cells

116

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“…An imbalance between the demand and capacity of the ER for protein folding is referred to as ER stress. Evidence is accumulating on the role of ER stress in the development of diabetes [105] and its complications, including retinopathy, nephropathy and neuropathy [106].…”

Section: Endoplasmic Reticulum Stressmentioning

confidence: 99%

Glucose Variability: How Does It Work?

Климонтов

Saik

Korbut

2021

IJMS

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A growing body of evidence points to the role of glucose variability (GV) in the development of the microvascular and macrovascular complications of diabetes. In this review, we summarize data on GV-induced biochemical, cellular and molecular events involved in the pathogenesis of diabetic complications. Current data indicate that the deteriorating effect of GV on target organs can be realized through oxidative stress, glycation, chronic low-grade inflammation, endothelial dysfunction, platelet activation, impaired angiogenesis and renal fibrosis. The effects of GV on oxidative stress, inflammation, endothelial dysfunction and hypercoagulability could be aggravated by hypoglycemia, associated with high GV. Oscillating hyperglycemia contributes to beta cell dysfunction, which leads to a further increase in GV and completes the vicious circle. In cells, the GV-induced cytotoxic effect includes mitochondrial dysfunction, endoplasmic reticulum stress and disturbances in autophagic flux, which are accompanied by reduced viability, activation of apoptosis and abnormalities in cell proliferation. These effects are realized through the up- and down-regulation of a large number of genes and the activity of signaling pathways such as PI3K/Akt, NF-κB, MAPK (ERK), JNK and TGF-β/Smad. Epigenetic modifications mediate the postponed effects of glucose fluctuations. The multiple deteriorative effects of GV provide further support for considering it as a therapeutic target in diabetes.

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“…The coincidence that both activities involved in the prenylation of RhoGTPases are associated with the ER raises the possibility that mechanical forces can modulate RhoGTPases through ER organization and the regulation of these PTM activities. These associations might also underpin a coupling between lipid metabolism (to which the ER is exquisitely sensitive) [176] and PTM regulation of Rho GTPases. In addition, some of the palmitoyltransferases are also localized in the ER, which can also be modulated by mechanical stretching [177,178].…”

Section: Rho Gtpases At the Nucleus: Trafficking And Functional Impactmentioning

confidence: 99%

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Navarro-Lérida

Sánchez-Álvarez

Pozo

2021

Cells

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Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

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A guide to understanding endoplasmic reticulum stress in metabolic disorders

Cited by 200 publications

References 206 publications

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Glucose Variability: How Does It Work?

Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

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