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TXNIP gene AND diabetes

Dae Hyun Kim, Seong Min Kim, Bonggi Lee, Eun Kyeong Lee, Ki Wung Chung, Kyoung Mi Moon, Hye Jin An, Kyung Mok Kim, Byung Pal Yu, Hae Young Chung
In the present study, we attempted to elucidate whether molecular modulation of inflammation by betaine through the forkhead box O1 (FOXO1)-induced NLRP3 inflammasome improves insulin resistance. Betaine is a major water-soluble component of Lycium chinense. It mainly functions as an oxidative metabolite of choline by suppressing superoxide-induced free radicals by donating methyl groups. The FOXO1 transcription factor regulates various genes involved in cellular metabolic processes related to cell death as well as oxidative stress responses through binding to the thioredoxin-interacting protein (TXNIP)...
April 22, 2017: Journal of Nutritional Biochemistry
Pradeep Bompada, David Atac, Cheng Luan, Robin Andersson, Judit Domènech Omella, Emilia Ottosson Laakso, Jason Wright, Leif Groop, Yang De Marinis
Thioredoxin-interacting protein (TXNIP) has been shown to be associated with glucose-induced deterioration of pancreatic beta cell function in diabetes. However, whether epigenetic mechanisms contribute to the regulation of TXNIP gene expression by glucose is not clear. Here we studied how glucose exerts its effect on TXNIP gene expression via modulation of histone acetylation marks. To achieve this, we applied clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) to knock out histone acetyltransferase (HAT) p300 in a rat pancreatic beta cell line INS1 832/13...
December 2016: International Journal of Biochemistry & Cell Biology
Karina Thieme, Karolline S Da Silva, Nelly T Fabre, Sergio Catanozi, Maria Beatriz Monteiro, Daniele Pereira Santos-Bezerra, Juliana Martins Costa-Pessoa, Maria Oliveira-Souza, Ubiratan F Machado, Marisa Passarelli, Maria Lucia Correa-Giannella
AIM: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC). METHODS: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed...
2016: Cellular Physiology and Biochemistry
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
Gemma Pujadas, Valeria De Nigris, Francesco Prattichizzo, Lucia La Sala, Roberto Testa, Antonio Ceriello
Dipeptidyl peptidase-4 inhibitors are widely used in type 2 diabetes. Endothelium plays a crucial role maintaining vascular integrity and function. Chronic exposure to high glucose drives to endothelial dysfunction generating oxidative stress. Teneligliptin is a novel dipeptidyl peptidase-4 inhibitor with antioxidant properties. This study is aimed to verify a potential protective action of teneligliptin in endothelial cells exposed to high glucose. Human umbilical vein endothelial cells were cultured under normal (5 mmol/L) or high glucose (25 mmol/L) during 21 days, or at high glucose during 14 days followed by 7 days at normal glucose, to reproduce the high-metabolic memory state...
June 2017: Endocrine
Xue-Bin Wang, Ya-di Han, Shuai Zhang, Ning-Hua Cui, Ze-Jin Liu, Zhu-Liang Huang, Cong Li, Fang Zheng
Single nucleotide polymorphisms (SNPs) in thioredoxin-interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two-stage case-control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype 'G-T' had a 1...
December 2016: Journal of Cellular and Molecular Medicine
Angélica Saraí Jiménez-Osorio, Susana González-Reyes, Wylly Ramsés García-Niño, Hortensia Moreno-Macías, Martha Eunice Rodríguez-Arellano, Gilberto Vargas-Alarcón, Joaquín Zúñiga, Rodrigo Barquera, José Pedraza-Chaverri
UNLABELLED: The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H: quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls...
2016: Oxidative Medicine and Cellular Longevity
Yara A Samra, Heba S Said, Nehal M Elsherbiny, Gregory I Liou, Mamdouh M El-Shishtawy, Laila A Eissa
AIMS: Hyperglycemia leads to elevation of oxidative stress and proinflammatory cytokines which are the main causes of diabetic nephropathy (DN). NLRP3 inflammasome and thioredoxin-interacting protein (TXNIP) are recently assumed to participate in the development of DN. We aimed to investigate the effects of Cepharanthine (CEP), Piperine (Pip) and their combination in streptozotocin (STZ)-induced DN focusing on their role to modulate NLRP3 and TXNIP induced inflammation. MAIN METHODS: Diabetic rats were treated with intraperitoneal (i...
July 15, 2016: Life Sciences
Yael Einbinder, Meital Ohana, Sydney Benchetrit, Tania Zehavi, Naomi Nacasch, Jacques Bernheim, Tali Zitman-Gal
BACKGROUND: Glucagon-like-peptide-1 (GLP-1) is a gut incretin hormone which stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol plays an important role in renal, endothelial, and cardiovascular protection. We evaluated the anti-inflammatory and histology effects of GLP-1 analogue (liraglutide) and calcitriol in a db/db mice diabetic model and in endothelial cells (EC) exposed to a diabetic-like environment. METHODS: Diabetic db/db mice were treated with liraglutide and calcitriol for 14 weeks, after which the kidneys were perfused and removed for mRNA and protein analysis and histology...
March 16, 2016: Diabetes/metabolism Research and Reviews
Yang De Marinis, Mengyin Cai, Pradeep Bompada, David Atac, Olga Kotova, Martin E Johansson, Eliana Garcia-Vaz, Maria F Gomez, Markku Laakso, Leif Groop
Diabetic kidney disease is the leading cause of end-stage renal disease. Genetic factors have been suggested to contribute to its susceptibility. However, results from genetic studies are disappointing possibly because the role of glucose in diabetic kidney disease predisposed by epigenetic mechanisms has not been taken into account. Since thioredoxin-interacting protein (TXNIP) has been shown to play an important role in the pathogenesis of diabetic kidney disease, we tested whether glucose could induce expression of TXNIP in the kidney by epigenetic mechanisms...
February 2016: Kidney International
Imari Mimura
Epigenetic mechanisms have been the focus of intensive research. De Marinis et al. demonstrated that high glucose levels exert stimulatory effects on activation histone marks, leading to the upregulation of thioredoxin-interacting protein (TXNIP) gene expression, which is proinflammatory. They also showed that the effect was reversed by the inhibition of histone acetyltransferase, suggesting a new therapeutic approach for improving diabetic kidney disease. Epigenetic changes are memorized as epigenetic memory that could exacerbate diabetic complications...
February 2016: Kidney International
Sara Mankoc Ramus, Ines Cilensek, Mojca Globocnik Petrovic, Miroslav Soucek, Peter Kruzliak, Daniel Petrovic
BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and its complications. The aim of this study was to examine the possible association between seven single nucleotide polymorphisms (SNPs) of the Trx2/TXNIP and TrxR2 genes encoding proteins involved in the thioredoxin antioxidant defence system and the risk of diabetic retinopthy (DR). DESIGN: Cross-sectional case-control study. PARTICIPANTS: A total of 802 Slovenian patients with Type 2 diabetes mellitus; 277 patients with DR and 525 with no DR were enrolled...
March 2016: Journal of Diabetes and its Complications
Daoyin Dong, Noah Fu, Peixin Yang
Pregestational diabetes significantly increases the risk of neural tube defects (NTDs). Maternal diabetes activates an Apoptosis Signal-regulating Kinase 1 (ASK1)-initiated pathway, which triggers neural stem cell apoptosis of the developing neuroepithelium leading to NTD formation. How high glucose of diabetes activates ASK1 is still unclear. In this study, we investigated the mechanism underlying high glucose-induced ASK1 activation. High glucose suppressed miR-17 expression, which led to an increase in its target gene Txnip (Thioredoxin-interacting protein)...
March 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer
Type 2 diabetes mellitus (DM) is an established risk factor for a wide range of vascular diseases, including ischemic stroke (IS). Glycated hemoglobin A1c (HbA1c), a marker for average blood glucose levels over the previous 12 weeks, is used as a measure of glycemic control and also as a diagnostic criterion for diabetes (HbA1c levels ≥ 6.5%). Epigenetic mechanisms, such as DNA methylation, may be associated with aging processes and with modulation of the risk of various pathologies, such as DM. Specifically, DNA methylation could be one of the mechanisms mediating the relation between DM and environmental exposures...
February 1, 2016: Human Molecular Genetics
Hui Yu, Xian-Xian Zhao, Xing-Hua Shan, Pan Li, Tao Chen
OBJECTIVE: To explore the regulatory role of thioredoxin-interacting protein (TXNIP) in Wnt/β-catenin signaling pathway and therefore to elucidate its function in diabetic myocardial infarction. METHODS: Diabetic myocardial infarction models were generated in mice. The expression levels of TXNIP and β-catenin and level of reactive oxygen species (ROS) were determined and compared with those in control group. Human umbilical vein endothelial cells were treated with high-concentration glucose and/or silencing TXNIP and/or H2O2...
November 2015: Asian Pacific Journal of Tropical Medicine
Ferhan S Siddiqi, Syamantak Majumder, Kerri Thai, Moustafa Abdalla, Pingzhao Hu, Suzanne L Advani, Kathryn E White, Bridgit B Bowskill, Giuliana Guarna, Claudia C Dos Santos, Kim A Connelly, Andrew Advani
Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions...
July 2016: Journal of the American Society of Nephrology: JASN
Maria Beatriz Monteiro, Daniele Pereira Santos-Bezerra, Karina Thieme, Sharon Nina Admoni, Ricardo Vessoni Perez, Cleide Guimarães Machado, Marcia Silva Queiroz, Marcia Nery, Maria Oliveira-Souza, Viktoria Woronik, Marisa Passarelli, Daniel Giannella-Neto, Ubiratan Fabres Machado, Maria Lúcia Corrêa-Giannella
AIMS: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications. METHODS: qPCR was employed to quantify target genes in urinary sediment (n = 55) and PBMC (n = 161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included...
2016: Free Radical Research
Ines Florath, Katja Butterbach, Jonathan Heiss, Melanie Bewerunge-Hudler, Yan Zhang, Ben Schöttker, Hermann Brenner
AIMS/HYPOTHESIS: Development of type 2 diabetes depends on environmental and genetic factors. We investigated the epigenome-wide association of prevalent diabetes with DNA methylation (DNAm) in peripheral blood. METHODS: DNAm was measured in whole blood with the Illumina Infinium HumanMethylation450 BeadChip in two subsamples of participants from the ESTHER cohort study. Cohort 1 included 988 participants, who were consecutively recruited between July and October 2000 and cohort 2 included 527 randomly selected participants...
January 2016: Diabetologia
Udayakumar Karunakaran, Jun Sung Moon, Hyoung Woo Lee, Kyu Chang Won
Diverse mechanisms are involved in the pathogenesis of β-cell failure in type 2 diabetes. Of them, the accumulation of ceramide, a bioactive lipid metabolite, is suggested to play a major role in inflammatory and stress responses that induce diabetes. However, the downstream inflammatory target of ceramide has not been defined. Using rat islets and the INS-1 β-cell line, we hypothesized that activation of the redox sensitive protein TXNIP is involved in ceramide-induced β-cell dysfunction. Incubation of INS-1 cells and primary islets with C2-ceramide (N-acetyl-sphingosine) downregulated insulin and PDX-1 expression and increased β-cell apoptosis...
November 2015: Biochimica et Biophysica Acta
Thomas Friedemann, Udo Schumacher, Yi Tao, Alexander Kai-Man Leung, Sven Schröder
Coptis chinensis rhizomes (CR) are one important ingredient of traditional Chinese herbal formulas such as San-Huang-Xie-Xin-Tang which is used for treatment of cardiovascular and neurodegenerative diseases. Recent studies suggest that the extract of CR might be a potential therapeutic agent for amelioration of neurological disorders associated with oxidative stress. In the present study we aimed at revealing the main active compound(s) of the CR extract and at investigating the mechanism of action. Four main alkaloids of the CR extract (berberine, coptisine, jatrorrhizine, and palmatine) were selected for this study...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
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