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er stress and diabetes

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https://www.readbyqxmd.com/read/28724746/therapeutic-targeting-tumor-progression-locus-2-tpl2-activating-transcription-factor-4-atf4-chemokine-stromal-cell-derived-factor-%C3%AE-sdf1%C3%AE-axis-suppresses-diabetic-retinopathy
#1
De-Wei Lai, Keng-Hung Lin, Wayne Huey-Herng Sheu, Maw-Rong Lee, Chung-Yu Chen, Wen-Jane Lee, Yi-Wen Hung, Chin-Chang Shen, Tsung-Ju Chung, Shing-Hwa Liu, Meei-Ling Sheu
Rationale: Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration and neovascularization. However, the mechanisms underlying the association between diabetes and progression retinopathy remain unclear. Objective: Tumor progression locus 2 (TPL2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of N(ε)-(carboxymethyl)lysine (CML), a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples...
July 19, 2017: Circulation Research
https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#2
REVIEW
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#3
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711624/curcumin-attenuates-oxidative-stress-induced-nf%C3%AE%C2%BAb-mediated-inflammation-and-endoplasmic-reticulum-dependent-apoptosis-of-splenocytes-in-diabetes
#4
Kahkashan Rashid, Sayantani Chowdhury, Sumit Ghosh, Parames C Sil
The present study was aimed to determine the curative role of curcumin against diabetes induced oxidative stress and its associated splenic complications. Diabetes was induced in the experimental rats via the intraperitoneal administration of a single dose of STZ (65 mg kg(-1) body weight). Increased blood glucose and intracellular ROS levels along with decreased body weight, the activity of cellular antioxidant enzymes and GSH/GSSG ratio were observed in the diabetic animals. Histological assessment showed white pulp depletion and damaged spleen anatomy in these animals...
July 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28698385/retinoic-acid-receptor-related-orphan-receptor-alpha-stimulates-adipose-tissue-inflammation-by-modulating-endoplasmic-reticulum-stress
#5
Yin Liu, Yulong Chen, Jinlong Zhang, Yulan Liu, Yanjie Zhang, Zhiguang Su
Adipose tissue inflammation has been linked to metabolic diseases such as obesity and type 2 diabetes. However, the molecules that mediate inflammation in adipose tissue have not been addressed. Although retinoic acid receptor-related orphan receptor alpha (RORα) is known to be involved in the regulation of inflammatory response in some tissues, its role is largely unknown in adipose tissue. Conversely, it is known that endoplasmic reticulum (ER) stress and unfolding protein response (UPR) signaling affect the inflammatory response in obese adipose tissue, but whether RORα regulates these processes remains unknown...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28698383/pancreatic-%C3%AE-cell-protection-from-inflammatory-stress-by-the-endoplasmic-reticulum-proteins-thrombospondin-1-and-mesencephalic-astrocyte-derived-neutrotrophic-factor-manf
#6
Daniel A Cunha, Monia Cito, Fabio A Grieco, Cristina Cosentino, Tatiana Danilova, Laurence Ladriere, Maria Lindahl, Andrii Domanskyi, Marco Bugliani, Piero Marchetti, Decio L Eizirik, Miriam Cnop
Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular mechanisms underlying pancreatic β-cell demise in type 1 diabetes. Thrombospondin-1 (THBS1) was recently shown to promote β-cell survival during lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat, mouse and human β-cells exposed to cytokines or thapsigargin-induced ER stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic astrocyte-derived neutrotrophic factor (MANF) in β-cells, and thereby prevents the BH3-only protein BIM-dependent triggering of the mitochondrial pathway of apoptosis...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28696246/farnesoid-x-receptor-agonism-protects-against-diabetic-tubulopathy-potential-add-on-therapy-for-diabetic-nephropathy
#7
Andi Marquardt, Moh'd Mohanad Al-Dabet, Sanchita Ghosh, Shrey Kohli, Jayakumar Manoharan, Ahmed ElWakiel, Ihsan Gadi, Fabian Bock, Sumra Nazir, Hongjie Wang, Jonathan A Lindquist, Peter Paul Nawroth, Thati Madhusudhan, Peter R Mertens, Khurrum Shahzad, Berend Isermann
Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28696115/discovery-of-a-benzamide-derivative-that-protects-pancreatic-%C3%AE-cells-against-endoplasmic-reticulum-stress
#8
Hongliang Duan, Yu Li, Daleep Arora, Depeng Xu, Hui-Ying Lim, Weidong Wang
Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing β-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of β-cell protective agents against ER stress-induced dysfunction and death. Through structure-activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects β-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 of 0...
July 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28684291/lysine-demethylase-inhibition-protects-pancreatic-%C3%AE-cells-from-apoptosis-and-improves-%C3%AE-cell-function
#9
Marie Balslev Backe, Jan Legaard Andersson, Karl Bacos, Dan Ploug Christensen, Jakob Bondo Hansen, Jerzy Jòzef Dorosz, Michael Gajhede, Tina Dahlby, Madhusudhan Bysani, Line Hyltoft Kristensen, Charlotte Ling, Lars Olsen, Thomas Mandrup-Poulsen
Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress. Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction...
July 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28681594/chop-deficiency-ameliorates-erk5-inhibition-mediated-exacerbation-of-streptozotocin-induced-hyperglycemia-and-pancreatic-beta-cell-apoptosis
#10
Dae-Hwan Nam, Jung-Hwa Han, Jae Hyang Lim, Kwon Moo Park, Chang-Hoon Woo
Streptozotocin (STZ)-induced murine models of type 1 diabetes have been used to examine ER stress during pancreatic beta- cell apoptosis, as this ER stress plays important roles in the pathogenesis and development of the disease. However, the mechanisms linking type 1 diabetes and the ER stressmodulating anti-diabetic signaling pathway remain to be addressed, though it was recently established that ERK5 (Extracellular- signal-regulated kinase 5) contributes to the pathogeneses of diabetic complications. This study was undertaken to explore the mechanism whereby ERK5 inhibition instigates pancreatic beta-cell apoptosis via an ER stress-dependent signaling pathway...
July 6, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28671608/lipotoxicity-induced-prmt1-exacerbates-mesangial-cell-apoptosis-via-endoplasmic-reticulum-stress
#11
Min-Jung Park, Ho Jae Han, Dong-Il Kim
Lipotoxicity-induced mesangial cell apoptosis is implicated in the exacerbation of diabetic nephropathy (DN). Protein arginine methyltransferases (PRMTs) have been known to regulate a variety of biological functions. Recently, it was reported that PRMT1 expression is increased in proximal tubule cells under diabetic conditions. However, their roles in mesangial cells remain unexplored. Thus, we examined the pathophysiological roles of PRMTs in mesangial cell apoptosis. Treatment with palmitate, which mimics cellular lipotoxicity, induced mesangial cell apoptosis via protein kinase RNA-like endoplasmic reticulum kinase (PERK) and ATF6-mediated endoplasmic reticulum (ER) stress signaling...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28630460/oxidative-and-endoplasmic-reticulum-stress-is-impaired-in-leukocytes-from-metabolically-unhealthy-vs-healthy-obese-individuals
#12
C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, A Blas-Garcia, S Veses, C Morillas, V M Victor, M Rocha, A Hernandez-Mijares
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO), and 31 had type 2 diabetes (MADO)...
June 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28606476/vitamin-d-supplement-ameliorates-hippocampal-metabolism-in-diabetic-rats
#13
Feng Guo, Hao Yue, Lei Wang, Chenzhao Ding, Lina Wu, Yang Wu, Fabao Gao, Guijun Qin
Vitamin D deficiency induced by diabetes mellitus is tightly associated with neurodegenerative diseases, but the mechanism is still unknown. Endoplasmic reticulum stress (ER stress) is involved in hippocampal lesion and promote diabetic neuropathy, so we focus on the effects of 1, 25-dihydroxy vitamin D3 on ER stress in hippocampus of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were administrated with different doses of vitamin D and divided into 3 groups: high, low, and blank, compared to wild-type rats which were received the same treatment...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28606465/ubiquitin-proteasome-system-and-er-stress-in-the-retina-of-diabetic-rats
#14
Karnam Shruthi, Singareddy Sreenivasa Reddy, Geereddy Bhanuprakash Reddy
PURPOSE: Diabetic retinopathy (DR) is the most frequently occurring complication of diabetes. Alterations in ubiquitin-proteasome system (UPS) have been associated with several degenerative disorders. Hence, in this study, we investigated the status and role of UPS and ER stress in the retina of diabetic rats. METHODS: Diabetes was induced in rats by streptozotocin. Retinal markers, ER stress markers, components of UPS, ERAD, and autophagy were analyzed after 2- and 4-months of diabetes...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28573503/endoplasmic-reticulum-stress-nrf2-signalling-and-cardiovascular-diseases-in-a-nutshell
#15
REVIEW
Chiara Mozzini, Luciano Cominacini, Ulisse Garbin, Anna Maria Fratta Pasini
PURPOSE OF REVIEW: This short review is intended primarily to summarize the understanding of the interrelated roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases. RECENT FINDINGS: Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced...
August 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28554128/mechanistic-insights-into-the-effects-of-quercetin-and-or-glp-1-analogue-liraglutide-on-high-fat-diet-streptozotocin-induced-type-2-diabetes-in-rats
#16
Hanaa H Gaballah, Soha S Zakaria, Shorouk E Mwafy, Nahid M Tahoon, Abla M Ebeid
BACKGROUND: The development of complementary treatment strategies that focuses on achieving a balance between adaptive and apoptotic unfolded protein response (UPR), enhancing endoplasmic reticulum (ER) homeostasis, and thus preserving β cell mass and function is particularly warranted. AIM: This study was designed to investigate the effectiveness of the combined treatment by Quercetin (QUE) and Liraglutide (LIRA) in modulating hyperglycemia, insulin-insensitivity, UPR/ER stress markers, apoptosis, oxidative stress and inflammation using a high-fat diet/streptozotocin -induced type 2 diabetic rat model...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28538869/potential-mechanisms-linking-probiotics-to-diabetes-a-narrative-review-of-the-literature
#17
Maryam Miraghajani, Somayeh Shahraki Dehsoukhteh, Nahid Rafie, Sahar Golpour Hamedani, Sima Sabihi, Reza Ghiasvand
CONTEXT AND OBJECTIVE: Some studies have suggested a wide range of possible mechanisms through which probiotics may play a role in diabetes prevention and treatment. However, the underlying mechanisms are not fully understood. We conducted this study to review the potential mechanisms suggested for the effect of probiotics in diabetes. DESIGN AND SETTING: Narrative review conducted at the Food Security Research Center of Isfahan. METHODS: A search in the electronic databases MEDLINE (PubMed), Cochrane Library, Web of Science and Google scholar was performed up to October 2016...
March 2017: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/28538172/using-hescs-to-probe-the-interaction-of-the-diabetes-associated-genes-cdkal1-and-mt1e
#18
Min Guo, Tuo Zhang, Xue Dong, Jenny Zhaoying Xiang, Minxiang Lei, Todd Evans, Johannes Graumann, Shuibing Chen
Genome-wide association studies (GWASs) have identified many disease-associated variant alleles, but understanding whether and how different genes/loci interact requires a platform for probing how the variant alleles act mechanistically. Isogenic mutant human embryonic stem cells (hESCs) provide an unlimited resource to derive and study human disease-relevant cells. Here, we focused on CDKAL1, linked by GWASs to diabetes. Through transcript profiling, we find that expression of the metallothionein (MT) gene family, also linked by GWASs to diabetes, is significantly downregulated in CDKAL1(-/-) cells that have been differentiated to insulin-expressing pancreatic beta-like cells...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28527893/chemistry-and-biology-of-reactive-species-with-special-reference-to-the-antioxidative-defence-status-in-pancreatic-%C3%AE-cells
#19
REVIEW
Sigurd Lenzen
BACKGROUND: Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. SCOPE REVIEW: This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28504910/fermented-moringa-oleifera-decreases-hepatic-adiposity-and-ameliorates-glucose-intolerance-in-high-fat-diet-induced-obese-mice
#20
Hyunchae Joung, Bobae Kim, Hyunjoon Park, Kyuyeon Lee, Hee-Hoon Kim, Ho-Cheol Sim, Hyun-Jin Do, Chang-Kee Hyun, Myoung-Sool Do
Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation...
May 2017: Journal of Medicinal Food
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