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er stress and diabetes

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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
#1
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...
May 17, 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
#2
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
https://www.readbyqxmd.com/read/28502979/chrysin-ameliorates-podocyte-injury-and-slit-diaphragm-protein-loss-via-inhibition-of-the-perk-eif2%C3%AE-atf-chop-pathway-in-diabetic-mice
#3
Min-Kyung Kang, Sin-Hye Park, Yun-Ho Kim, Eun-Jung Lee, Lucia Dwi Antika, Dong Yeon Kim, Yean-Jung Choi, Young-Hee Kang
Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys...
May 15, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28497987/elevated-activating-transcription-factor-4-and-glucose-regulated-78-kda-protein-levels-correlate-with-inflammatory-cytokines-in-the-aqueous-humor-and-vitreous-of-proliferative-diabetic-retinopathy
#4
Yanuo Wang, Sha Gao, Yanji Zhu, Xi Shen
PURPOSE: To determine concentrations of endoplasmic reticulum (ER) stress-related factors activating transcription factor 4 (ATF4) and glucose-regulated 78 kDa protein (GRP78) in vitreous and aqueous humor (AqH) of patients with proliferative diabetic retinopathy (PDR) and the correlation of ATF4, GRP78 and inflammatory cytokines interleukin-6(IL-6) and monocyte chemoattractant protein-1 (MCP-1). MATERIALS AND METHODS: AqH and vitreous samples were collected from eyes of patients with PDR and idiopathic macular hole (IMH) which needed vitrectomy...
May 12, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28487366/temporal-characterization-of-%C3%AE-cell-adaptive-and-maladaptive-mechanisms-during-chronic-high-fat-feeding-in-c57bl-6ntac-mice
#5
Dhananjay Gupta, Thomas L Jetton, Kyla LaRock, Navjot Monga, Basanthi Satish, James Lausier, Mina Peshavaria, John L Leahy
The onset of type 2 diabetes is characterized by transition from successful to failed insulin secretory compensation to obesity-related insulin resistance and dysmetabolism. Energy-rich diets in rodents are commonly-studied models of compensatory increases in both insulin secretion and β-cell mass. However, the mechanisms of these adaptive responses are incompletely understood, and it is also unclear why these responses eventually fail. We measured the temporal trends of glucose homeostasis, insulin secretion, β-cell morphometry, and islet gene expression in C57BL/6NTac mice fed a 60% high fat (HFD) or control diet for up to 16 weeks...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484241/glial-cell-line-derived-neurotrophic-factor-protects-human-islets-from-nutrient-deprivation-and-endoplasmic-reticulum-stress-induced-apoptosis
#6
Shadab Abadpour, Sven O Göpel, Simen W Schive, Olle Korsgren, Aksel Foss, Hanne Scholz
One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28482072/endoplasmic-reticulum-stress-induced-chop-inhibits-pgc-1%C3%AE-and-causes-mitochondrial-dysfunction-in-diabetic-embryopathy
#7
Xi Chen, Jianxiang Zhong, Daoyin Dong, Gentao Liu, Peixin Yang
Endoplasmic reticulum (ER) stress has been implicated in the development of maternal diabetes-induced neural tube defects (NTDs). ER stress-induced C/EBP homologous protein (CHOP) plays an important role in the pro-apoptotic execution pathways. However, the molecular mechanism underlying ER stress- and CHOP-induced neuroepithelium cell apoptosis in diabetic embryopathy are still unclear. Deletion of the Chop gene significantly reduced maternal diabetes-induced NTDs. CHOP deficiency abrogated maternal diabetes-induced mitochondrial dysfunction and neuroepithelium cell apoptosis...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28476623/syringin-attenuates-insulin-resistance-via-adiponectin-mediated-suppression-of-low-grade-chronic-inflammation-and-er-stress-in-high-fat-diet-fed-mice
#8
Bobae Kim, Min-Seok Kim, Chang-Kee Hyun
In the treatment of type 2 diabetes, improvements in glucose control are often linked to side effects such as weight gain and altered lipid metabolism, increasing the risk of cardiovascular disease. It is therefore important to develop antidiabetic drugs that exert beneficial effects on insulin sensitivity and lipid metabolism at the same time. Here we demonstrate that syringin, a naturally occurring glucoside, improves glucose tolerance without increased weight gain in high-fat diet-induced obese mice. Syringin augmented insulin-stimulated Akt phosphorylation in skeletal muscle, epididymal adipose tissue (EAT), and the liver, showing an insulin-sensitizing activity...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28473471/are-targeted-therapies-for-diabetic-cardiomyopathy-on-the-horizon
#9
REVIEW
Mitchel Tate, David J Grieve, Rebecca H Ritchie
Diabetes increases the risk of heart failure approximately 2.5-fold, independent of coronary artery disease and other comorbidities. This process, termed diabetic cardiomyopathy, is characterized by initial impairment of left ventricular (LV) relaxation followed by LV contractile dysfunction. Post-mortem examination reveals that human diastolic dysfunction is closely associated with LV damage, including cardiomyocyte hypertrophy, apoptosis and fibrosis, with impaired coronary microvascular perfusion. The pathophysiological mechanisms underpinning the characteristic features of diabetic cardiomyopathy remain poorly understood, although multiple factors including altered lipid metabolism, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, as well as epigenetic changes, are implicated...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28470097/phenylbutyrate-and-%C3%AE-cell-function-contribution-of-histone-deacetylases-and-er-stress-inhibition
#10
Sabbir Khan, Sandeep K Komarya, Gopabandhu Jena
Incidences of diabetes are increasing globally due to involvement of genetic and epigenetic factors. Phenylbutyrate (PBA) is a US FDA approved drug for treatment of urea cycle disorder in children. PBA reduces endoplasmic reticulum (ER) stress and is proven as a potent histone deacetylases (HDACs) inhibitor. Chronic ER stress results in unfolding protein response, which triggers apoptosis. Abnormal ER homoeostasis is responsible for defective processing of several genes/proteins and contributes to β-cell death/failure...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28468959/dominant-er-stress-inducing-wfs1-mutations-underlie-a-genetic-syndrome-of-neonatal-infancy-onset-diabetes-congenital-sensorineural-deafness-and-congenital-cataracts
#11
Elisa De Franco, Sarah E Flanagan, Takuya Yagi, Damien Abreu, Jana Mahadevan, Matthew B Johnson, Garan Jones, Fernanda Acosta, Mphele Mulaudzi, Ngee Lek, Vera Oh, Oliver Petz, Richard Caswell, Sian Ellard, Fumihiko Urano, Andrew T Hattersley
Neonatal diabetes is frequently part of a complex syndrome with extra-pancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There remain patients with neonatal diabetes who have novel genetic syndromes.We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic aetiology of a syndrome characterized by neonatal diabetes, sensorineural deafness and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded...
May 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28467938/targeting-abl-ire1%C3%AE-signaling-spares-er-stressed-pancreatic-%C3%AE-cells-to-reverse-autoimmune-diabetes
#12
Shuhei Morita, S Armando Villalta, Hannah C Feldman, Ames C Register, Wendy Rosenthal, Ingeborg T Hoffmann-Petersen, Morvarid Mehdizadeh, Rajarshi Ghosh, Likun Wang, Kevin Colon-Negron, Rosa Meza-Acevedo, Bradley J Backes, Dustin J Maly, Jeffrey A Bluestone, Feroz R Papa
No abstract text is available yet for this article.
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28466490/local-and-regional-control-of-calcium-dynamics-in-the-pancreatic-islet
#13
REVIEW
Guy A Rutter, David J Hodson, Pauline Chabosseau, Elizabeth Haythorne, Timothy J Pullen, Isabelle Leclerc
Ca(2+) is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K(+) channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca(2+) changes. Voltage-gated Ca(2+) channels, Ca(2+) -activated K(+) channels and Na(+) /Ca(2+) exchange all play important roles. The use of targeted Ca(2+) probes has revealed that during each cytosolic Ca(2+) pulse, uptake of Ca(2+) by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca(2+) dynamics and control organellar function...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28465244/perk-eif2%C3%AE-contributes-to-changes-of-insulin-signaling-in-hepg2-cell-induced-by-intermittent-hypoxia
#14
Huahua Yi, Chenjuan Gu, Min Li, Zhiguo Zhang, Qingyun Li, Jing Feng, Jun Zhou, Juan Du
AIMS: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with abnormal glucose metabolism. Nowadays, endoplasmic reticulum (ER) stress emerges as an important mechanism underlying the development of type 2 diabetes mellitus (T2DM). However, it remains unclear that intermittent hypoxia (IH) could induce ER stress, resulting in abnormality of glucose metabolism. Thu, in the current study we explore the changes of insulin signaling under IH and the role of ER stress underlying these changes...
April 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/28461456/elovl6-deficiency-improves-glycemic-control-in-diabetic-db-db-mice-by-expanding-%C3%AE-cell-mass-and-increasing-insulin-secretory-capacity
#15
Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Kaori Motomura, Nie Tang, Tomotaka Yokoo, Yuka Okajima, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano
Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of β-cell dysfunction and loss of β-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D...
May 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28455824/diallyl-trisulfide-ameliorates-myocardial-ischemia-reperfusion-injury-by-reducing-oxidative-stress-and-endoplasmic-reticulum-stress-mediated-apoptosis-in-type-1-diabetic-rats-role-of-sirt1-activation
#16
Liming Yu, Shu Li, Xinlong Tang, Zhi Li, Jian Zhang, Xiaodong Xue, Jinsong Han, Yu Liu, Yuji Zhang, Yong Zhang, Yinli Xu, Yang Yang, Huishan Wang
Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg)...
April 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#17
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#18
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28436023/activation-of-amp-activated-protein-kinase-by-metformin-ablates-angiotensin-ii-induced-endoplasmic-reticulum-stress-and-hypertension-in-mice-in-vivo
#19
Quanlu Duan, Ping Song, Ye Ding, Ming-Hui Zou
BACKGROUND AND PURPOSE: Metformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts blood pressure (BP)-lowering effects in patients with diabetes; however, the effects and underlying mechanisms of metformin on BP in non-diabetic condition remains to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The effects of metformin on BP were investigated in wild-type (WT, C57BL/6 J) and AMP-activated protein kinase (AMPKα2) knockout (AMPKα2(-/-) ) mice with or without Ang II-infusion...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432299/tangluoning-a-traditional-chinese-medicine-attenuates-in-vivo-and-in-vitro-diabetic-peripheral-neuropathy-through-modulation-of-perk-nrf2-pathway
#20
Xinwei Yang, Weijie Yao, Haolong Liu, Yanbin Gao, Renhui Liu, Liping Xu
Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose...
April 21, 2017: Scientific Reports
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