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er stress and diabetes

H Viisanen, H Chapman, H Wei, M Lasierra Losada, A Koivisto, K E Akerman, A Pertovaara
Methylglyoxal (MG) is a reactive carbonyl compound generated in diabetes mellitus. MG is an established transient receptor potential ankyrin 1 (TRPA1) channel agonist that contributes to TRPA1-mediated diabetic pain hypersensitivity. Here we studied whether exposure to diabetes and thereby to elevated endogenous MG modulates hypersensitivity induced by intradermal MG. Moreover, since diabetes induces endoplasmic reticulum (ER) stress, we compared the role of TRPA1 in diabetes and ER stress by assessing whether tunicamycin-induced ER stress, without diabetes, produces TRPA1-mediated pain hypersensitivity and by assessing whether ER stress and diabetes have similar modulatory effects on MG-induced hypersensitivity...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Dilip Sharma, Jitendra Narain Singh, Shyam S Sharma
Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding...
October 21, 2016: Neuroscience Letters
Yoon Young Choi, Suji Kim, Jung-Hwa Han, Dae-Hwan Nam, Kwon Moo Park, Seong Yong Kim, Chang-Hoon Woo
Epidemiological studies suggested that diabetic patients are susceptible to develop cardiovascular complications along with having endothelial dysfunction. It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction rather than glucose itself. Here, we investigated the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress. Biochemical data showed that 4-PBA significantly inhibited MGO-induced protein cleavages of PARP-1 and caspase-3...
October 18, 2016: Biochemical and Biophysical Research Communications
Mahalingam Balakumar, Durai Prabhu, Chandrakumar Sathishkumar, Paramasivam Prabu, Namita Rokana, Ramesh Kumar, Srividhya Raghavan, Avinash Soundarajan, Sunita Grover, Virender Kumar Batish, Viswanathan Mohan, Muthuswamy Balasubramanyam
PURPOSE: Diabetes and obesity are characterized by glucose intolerance, fat deposition, inflammation, and dyslipidemia. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects and modulating gut microbiota beneficially through specific probiotics could be a potential therapeutic option for type 2 diabetes/obesity. Therefore, we attempted to study the efficacy of probiotics of Indian gut origin (Lactobacillus plantarum MTCC5690 and Lactobacillus fermentum MTCC5689) along with a positive control, Lactobacillus rhamnosus (LGG) on glucose/lipid homeostasis in high-fat-diet-induced diabetic animal model...
October 18, 2016: European Journal of Nutrition
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris
Pancreatic dysfunction during diabetes is linked to the induction of endoplasmic reticulum (ER) stress on pancreatic beta (β) cells. Our laboratory recently discovered that p21 protects from diabetes by modifying the outcome of ER stress response. In the present study, we explored the antidiabetic activity of ciclopirox (CPX), an iron chelator and recently described activator of p21 expression. The effects of CPX in beta cell survival and function were assessed in cultured islets in vitro as well as in diabetic mice in vivo...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Soo-Kyeong Song, Sang-Rok Lee, Lae-Young Jung, Yi-Shik Kim, Sun-Hwa Lee, Kyoung-Suk Rhee, Jei-Keon Chae, Won-Ho Kim, Jae-Ki Ko
OBJECTIVE: Wall shear stress contributes to atherosclerosis progression and plaque rupture. There were limited studies for hypertension as influence factor on whole blood viscosity (WBV) in acute coronary syndrome (ACS) patients. We evaluated the relations between WBV and hypertension in patients who visited to the emergency room by acute chest pain. DESIGN AND METHOD: From April 2013 through June 2015, we prospectively enrolled 471 acute chest pain patients who visited emergency room...
September 2016: Journal of Hypertension
L Ozcan, I Tabas
The burden of type 2 diabetes and its major complication cardiovascular disease is rapidly increasing worldwide. Understanding the underlying pathogenic mechanisms of these diseases is crucial to develop novel therapeutics. Recent work using genetic and biochemical methods in mouse models and human samples have identified disturbed calcium signalling and endoplasmic reticulum stress as emerging factors involved in the pathogenesis of many metabolic diseases. In this review, we will highlight the specific roles of calcium signalling and endoplasmic reticulum stress response in the development of insulin resistance and atherosclerosis...
October 14, 2016: Journal of Internal Medicine
Amy L Clark, Fumihiko Urano
Type 1 diabetes results from the autoimmune destruction of pancreatic β cells, leading to insulin deficiency and hyperglycemia. Although multiple attempts have been made to slow the autoimmune process using immunosuppressive or immunomodulatory agents, there are still no effective treatments that can delay or reverse the progression of type 1 diabetes in humans. Recent studies support endoplasmic reticulum (ER) as a novel target for preventing the initiation of the autoimmune reaction, propagation of inflammation, and β cell death in type 1 diabetes...
October 5, 2016: Current Opinion in Immunology
M Balakumar, L Raji, D Prabhu, C Sathishkumar, P Prabu, V Mohan, M Balasubramanyam
In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet...
October 3, 2016: Molecular and Cellular Biochemistry
Christian Klingler, Xinjie Zhao, Till Adhikary, Jia Li, Guowang Xu, Hans-Ulrich Häring, Erwin Schleicher, Rainer Lehmann, Cora Weigert
Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10μM LPC for 24h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A...
September 30, 2016: Biochimica et Biophysica Acta
Marcel Doerflinger, Jason Glab, Christina Nedeva, Irvin Jose, Ann Lin, Lorraine O'Reilly, Cody Allison, Marc Pellegrini, Richard S Hotchkiss, Hamsa Puthalakath
Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte death during polymicrobial sepsis, which was reproducible in in vivo mouse models. Modulating ER stress using chemical chaperones significantly reduced the induction of the pro-apoptotic protein Bim both in vitro and in mice...
October 3, 2016: Scientific Reports
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
Min Ye, Weiqin Lu, Xiaojie Wang, Cong Wang, James L Abbruzzese, Guang Liang, Xiaokun Li, Yongde Luo
The anti-obese and anti-diabetic FGF21 regulates lipid metabolism and energy homeostasis by targeting the betaKlotho-FGFR1 binary complex in adipose tissue adipocytes. Since lipid droplet is the organelle responsible for storing lipid energy in adipocytes, it is the plausible target of FGF21 action. However, the impact of the FGF21-betaKlotho-FGFR1 signaling pathway on the functions of the lipid droplet is not clearly understood. Using our mouse models of adipocyte-specific FGFR1 ablation and hepatic overexpression of FGF21 with diet-induced obesity established previously, we analyzed the alterations of the pathways involved in energy and substrate metabolism that is attributable to the dynamic functions of the lipid droplet...
October 3, 2016: Endocrinology
Mitsuo Kato, Mei Wang, Zhuo Chen, Kirti Bhatt, Hyung Jung Oh, Linda Lanting, Supriya Deshpande, Ye Jia, Jennifer Y C Lai, Christopher L O'Connor, YiFan Wu, Jeffrey B Hodgin, Robert G Nelson, Markus Bitzer, Rama Natarajan
It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including renal extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that a megacluster of nearly 40 microRNAs and their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli of mouse models of DN, and mesangial cells treated with transforming growth factor-β1 (TGF- β1) or high glucose...
2016: Nature Communications
Jing Zhang, Ying Fan, Chuchu Zeng, Li He, Niansong Wang
Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology...
2016: Nutrients
Chih-Kang Chiang, Ching-Chia Wang, Tien-Fong Lu, Kuo-How Huang, Meei-Ling Sheu, Shing-Hwa Liu, Kuan-Yu Hung
Advanced glycation end-products (AGEs)-induced mesangial cell death is one of major causes of glomerulus dysfunction in diabetic nephropathy. Both endoplasmic reticulum (ER) stress and autophagy are adaptive responses in cells under environmental stress and participate in the renal diseases. The role of ER stress and autophagy in AGEs-induced mesangial cell death is still unclear. Here, we investigated the effect and mechanism of AGEs on glomerular mesangial cells. AGEs dose-dependently decreased mesangial cell viability and induced cell apoptosis...
September 26, 2016: Scientific Reports
Juan Chen, Xue-Feng Hou, Gang Wang, Qing-Xiang Zhong, Ying Liu, Hui-Hui Qiu, Nan Yang, Jun-Fei Gu, Chun-Fei Wang, Li Zhang, Jie Song, Lu-Qi Huang, Xiao-Bin Jia, Ming-Hua Zhang, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN...
September 21, 2016: Journal of Ethnopharmacology
Jun Sung Moon, Udayakumar Karunakaran, Suma Elumalai, In-Kyu Lee, Hyoung Woo Lee, Yong-Woon Kim, Kyu Chang Won
AIM/HYPOTHESIS: Cluster determinant 36 (CD36), a fatty acid transporter, was reported to have a pivotal role in glucotoxicity-induced beta cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression, and it is unknown whether this action can be counteracted by metformin. In the present study, we showed that metformin counteracts glucotoxicity by alleviating oxidative and endoplasmic reticulum (ER) stress-induced CD36 expression. METHODS: We used primary rat islets as well as INS-1 cells for 72h to 24h with 30mM glucose, respectively...
September 9, 2016: Journal of Diabetes and its Complications
Yuan Lu, Qiong-Qiong Xing, Jian-Ya Xu, Dou Ding, Xia Zhao
Endoplasmic reticulum (ER) stress has been recently revealed to play a pivotal role in the pathogenesis of severe asthma. Astragalus polysaccharide (APS), a major bioactive component from Astragalus membranaceus, exerts immunomodulatory and anti-inflammatory effects and has been shown to suppress ER stress in chronic diseases such as type-2 diabetes. However, the pharmaceutical application of APS in the treatment of severe asthma is unknown. The results obtained here indicate that APS significantly attenuates eosinophils and neutrophil-dominant airway inflammation by reducing the mRNA levels of Cxcl5, Il8, and chemokine (C-C motif) ligand 20 (Ccl20) and the protein levels of IL13RA and IL17RA...
September 16, 2016: International Journal of Biological Macromolecules
Soo-Kyeong Song, Sang-Rok Lee, Lae-Young Jung, Yi-Shik Kim, Sun-Hwa Lee, Kyoung-Suk Rhee, Jei-Keon Chae, Won-Ho Kim, Jae-Ki Ko
OBJECTIVE: Wall shear stress contributes to atherosclerosis progression and plaque rupture. There were limited studies for hypertension as influence factor on whole blood viscosity (WBV) in acute coronary syndrome (ACS) patients. We evaluated the relations between WBV and hypertension in patients who visited to the emergency room by acute chest pain. DESIGN AND METHOD: From April 2013 through June 2015, we prospectively enrolled 471 acute chest pain patients who visited emergency room...
September 2016: Journal of Hypertension
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