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https://www.readbyqxmd.com/read/29769440/elevated-hepatic-expression-of-h19-long-noncoding-rna-contributes-to-diabetic-hyperglycemia
#1
Na Zhang, Tingting Geng, Zhangsheng Wang, Ruling Zhang, Tiefeng Cao, Joao Paulo Camporez, Shi-Ying Cai, Ya Liu, Luisa Dandolo, Gerald I Shulman, Gordon G Carmichael, Hugh S Taylor, Yingqun Huang
Excessive hepatic glucose production (HGP) contributes significantly to the hyperglycemia of type 2 diabetes; however, the molecular mechanism underlying this dysregulation remains poorly understood. Here, we show that fasting temporally increases the expression of H19 long noncoding RNA (lncRNA) in nondiabetic mouse liver, whereas its level is chronically elevated in diet-induced diabetic mice, consistent with the previously reported chronic hepatic H19 increase in diabetic patients. Importantly, liver-specific H19 overexpression promotes HGP, hyperglycemia, and insulin resistance, while H19 depletion enhances insulin-dependent suppression of HGP...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29758564/monogenic-diabetes-in-overweight-and-obese-youth-diagnosed-with-type-2-diabetes-the-today-clinical-trial
#2
Jeffrey W Kleinberger, Kenneth C Copeland, Rachelle G Gandica, Morey W Haymond, Lynne L Levitsky, Barbara Linder, Alan R Shuldiner, Sherida Tollefsen, Neil H White, Toni I Pollin
PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).MethodsSequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial...
October 12, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29747153/molecular-characterization-of-colorectal-signet-ring-cell-carcinoma-using-whole-exome-and-rna-sequencing
#3
Jae-Yong Nam, Bo Young Oh, Hye Kyung Hong, Joon Seol Bae, Tae Won Kim, Sang Yun Ha, Donghyun Park, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yoon Ah Park, Je-Gun Joung, Woong-Yang Park, Yong Beom Cho
BACKGROUND: Signet-ring cell carcinoma (SRCC) is a very rare subtype of colorectal adenocarcinoma (COAD) with a poor clinical prognosis. Although understanding key mechanisms of tumor progression in SRCCs is critical for precise treatment, a comprehensive view of genomic alterations is lacking. MATERIALS AND METHODS: We performed whole-exome sequencing of tumors and matched normal blood as well as RNA sequencing of tumors and matched normal colonic tissues from five patients with SRCC...
May 7, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29740493/bioinformatic-analysis-and-prediction-of-the-function-and-regulatory-network-of-long-non-coding-rnas-in-hepatocellular-carcinoma
#4
Ming-Rong Cao, Ze-Ping Han, Ji-Ming Liu, Yu-Guang Li, Yu-Bing Lv, Jia-Bin Zhou, Jin-Hua He
Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29739729/congenital-hyperinsulinism-and-evolution-to-sulfonylurea-responsive-diabetes-later-in-life-due-to-a-novel-homozygous-p-l171f-abcc8-mutation
#5
Emregül Işık, Huseyin Demirbilek, Jayne A L Houghton, Sian Ellard, Sarah E Flanagan, Khalid Hussain
BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50 % of all CHI cases. Hyperinsulinaemic hypoglycaemia (HH) in infancy and diabetes in later life have been reported in subjects with HNF1A , HNF4A and ABCC8 mutations. CASE REPORT: Herein, we present a child who was diagnosed with CHI at birth, then developed diabetes mellitus at the age of 9 years due to a novel homozygous missense, p...
March 29, 2018: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29726111/clinical-usefulness-of-comprehensive-genetic-screening-in-mody-a-novel-abcc8-mutation-in-a-previously-screened-family
#6
Stephanie Robyn Johnson, Paul Leo, Louise Sonia Conwell, Mark Harris, Matthew Arthur Brown, Emma Letitia Duncan
Maturity-onset diabetes of the young (MODY) is the commonest form of monogenic diabetes, resulting from dominant mutations in one of fourteen genes that regulate beta-cell function (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8,KCNJ11 and APPL1 1,2 ). MODY accounts for 2-2.5% of childhood diabetes 3 , yet MODY genetic screening is uncommon, even in highly suggestive families, and when performed often limited to the commonest genes (e.g.HNF1A and GCK) 4 .
May 4, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29708925/unexplained-reciprocal-regulation-of-diabetes-and-lipoproteins
#7
Sei Higuchi, M Concepción Izquierdo, Rebecca A Haeusler
PURPOSE OF REVIEW: Type 2 diabetes is associated with a characteristic dyslipidemia that may exacerbate cardiovascular risk. The causes of, and the effects of new antihyperglycemia medications on, this dyslipidemia, are under investigation. In an unexpected reciprocal manner, lowering LDL-cholesterol with statins slightly increases the risk of diabetes. Here we review the latest findings. RECENT FINDINGS: The inverse relationship between LDL-cholesterol and diabetes has now been confirmed by multiple lines of evidence...
June 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29672926/insights-into-the-etiology-associated-gene-regulatory-networks-in-hepatocellular-carcinoma-from-the-cancer-genome-atlas
#8
Veerabrahma Pratap Seshachalam, Karthik Sekar, Kam M Hui
BACKGROUND AND AIM: Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. METHODS: Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation...
April 19, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29626713/differentiation-of-hepatocyte-like-cells-from-human-pluripotent-stem-cells-using-small-molecules
#9
Faizal Z Asumda, Konstantinos E Hatzistergos, Derek M Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R Schiff
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives...
March 27, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29598821/association-between-the-dna-methylations-of-pomc-mc4r-and-hnf4a-and-metabolic-profiles-in-the-blood-of-children-aged-7-9-years
#10
Eun Jin Kwon, Young-Ah You, Bohyun Park, Eun Hee Ha, Hae Soon Kim, Hyesook Park, Young Ju Kim
BACKGROUND: Proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), and hepatocyte nuclear factor 4 alpha (HNF4A) are closely associated with weight gain and metabolic traits. In a previous study, we demonstrated associations between the methylations of POMC, MC4R, and HNF4A and metabolic profiles at birth. However, little is known about these associations in obese children. To evaluate the clinical utility of epigenetic biomarkers, we investigated to determine whether an association exists between the methylations of POMC, MC4R, and HNF4A and metabolic profiles in blood of normal weight and overweight and obese children...
March 29, 2018: BMC Pediatrics
https://www.readbyqxmd.com/read/29567659/genetic-drivers-of-pancreatic-islet-function
#11
Mark P Keller, Daniel M Gatti, Kathryn L Schueler, Mary E Rabaglia, Donnie S Stapleton, Petr Simecek, Matthew Vincent, Sadie Allen, Aimee Teo Broman, Rhonda Bacher, Christina Kendziorski, Karl W Broman, Brian S Yandell, Gary A Churchill, Alan D Attie
The majority of gene loci that have been associated with type 2 diabetes play a role in pancreatic islet function. To evaluate the role of islet gene expression in the etiology of diabetes, we sensitized a genetically diverse mouse population with a Western diet high in fat (45%-kcal) and sucrose (34%) and carried out genome-wide association mapping of diabetes-related phenotypes. We quantified mRNA abundance in the islets and identified 18,820 expression quantitative trait loci. We applied mediation analysis to identify candidate causal driver genes at loci that affect the abundance of numerous transcripts...
March 22, 2018: Genetics
https://www.readbyqxmd.com/read/29556568/gastric-cancer-biomarkers-a-systems-biology-approach
#12
Mohammad Saberi Anvar, Zarrin Minuchehr, Mohsen Shahlaei, Samira Kheitan
Gastric cancer is one of the most fatal cancers in the world. Many efforts in recent years have attempted to find effective proteins in gastric cancer. By using a comprehensive list of proteins involved in gastric cancer, scientists were able to retrieve interaction information. The study of protein-protein interaction networks through systems biology based analysis provides appropriate strategies to discover candidate proteins and key biological pathways. In this study, we investigated dominant functional themes and centrality parameters including betweenness as well as the degree of each topological clusters and expressionally active sub-networks in the resulted network...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29546319/lineage-specification-revealed-by-single-cell-gene-expression-analysis-in-porcine-preimplantation-embryos
#13
Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29534881/tumor-promoting-cyanotoxin-microcystin-lr-does-not-induce-procarcinogenic-events-in-adult-human-liver-stem-cells
#14
Jan Raska, Lucie Ctverackova, Aneta Dydowiczova, Iva Sovadinova, Ludek Blaha, Pavel Babica
HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, α-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed...
March 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29493090/clinical-heterogeneity-of-hyperinsulinism-due-to-hnf1a-and-hnf4a-mutations
#15
Joanna Yuet-Ling Tung, Kara Boodhansingh, Charles A Stanley, Diva D De León
BACKGROUND: Dominant inactivating mutations in HNF1A and HNF4A have been described to cause hyperinsulinism (HI) before evolving to diabetes. However, information available in the literature regarding the clinical phenotype is limited. OBJECTIVE: To report the prevalence of HNF1A and HNF4A mutations in a large cohort of children with HI, and to describe their genotypes and phenotypes. DESIGN: Retrospective descriptive study. METHODS: Medical records were reviewed to extract clinical information...
March 1, 2018: Pediatric Diabetes
https://www.readbyqxmd.com/read/29475831/sleeve-gastrectomy-improves-glycemia-independent-of-weight-loss-by-restoring-hepatic-insulin-sensitivity
#16
Samir Abu Gazala, Elad Horwitz, Rachel Ben-Haroush Schyr, Aya Bardugo, Hadar Israeli, Ayat Hija, Jonathan Schug, Soona Shin, Yuval Dor, Klaus H Kaestner, Danny Ben-Zvi
Bariatric surgery dramatically improves glycemic control, yet the underlying molecular mechanisms remain controversial due to confounding weight loss. We performed sleeve gastrectomy (SG) on obese and diabetic leptin receptor-deficient mice ( db / db ). One week post-surgery, mice weighed 5% less and displayed improved glycemia compared to sham-operated controls and islets from SG mice displayed reduced expression of diabetes markers. One month post-surgery SG mice weighed more than pre-operatively, but remained near-euglycemic and displayed reduced hepatic lipid droplets...
February 23, 2018: Diabetes
https://www.readbyqxmd.com/read/29466743/a-roadmap-for-human-liver-differentiation-from-pluripotent-stem-cells
#17
Lay Teng Ang, Antson Kiat Yee Tan, Matias I Autio, Su Hua Goh, Siew Hua Choo, Kian Leong Lee, Jianmin Tan, Bangfen Pan, Jane Jia Hui Lee, Jen Jen Lum, Christina Ying Yan Lim, Isabelle Kai Xin Yeo, Chloe Jin Yee Wong, Min Liu, Jueween Ling Li Oh, Cheryl Pei Lynn Chia, Chet Hong Loh, Angela Chen, Qingfeng Chen, Irving L Weissman, Kyle M Loh, Bing Lim
How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29450745/clinical-management-of-women-with-monogenic-diabetes-during-pregnancy
#18
REVIEW
Laura T Dickens, Rochelle N Naylor
PURPOSE OF REVIEW: Monogenic diabetes accounts for 1-2% of all diabetes cases, but is frequently misdiagnosed as type 1, type 2, or gestational diabetes. Accurate genetic diagnosis directs management, such as no pharmacologic treatment for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose sulfonylureas for KATP channel-related diabetes. While diabetes treatment is defined for the most common causes of monogenic diabetes, pregnancy poses a challenge to management...
February 15, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29408271/maturity-onset-diabetes-of-the-young-mody-in-tunisia-low-frequencies-of-gck-and-hnf1a-mutations
#19
S Ben Khelifa, R Martinez, A Dandana, I Khochtali, S Ferchichi, L Castaño
Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, an early clinical onset and a primary defect in β-cell function. Mutations in the GCK and HNF1A genes are the most common cause of MODY among Caucasians. The etiology of MODY in Tunisia stills a challenge for researchers. The aim of this study was to screen for mutations in GCK, HNF1A, HNF4A and INS genes in North African Tunisians subjects, in whom the clinical profile was very suggestive of MODY...
April 20, 2018: Gene
https://www.readbyqxmd.com/read/29404444/hairy-and-enhancer-of-split-6-prevents-hepatic-lipid-accumulation-through-inhibition-of-pparg2-expression
#20
Jung Eun Park, Mikang Lee, Seong-Chul Kim, Yanqiao Zhang, James P Hardwick, Yoon Kwang Lee
Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARγ2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of Pparg2 expression and hepatic steatosis induced by diet. Liver-specific overexpression of Hes6 using adenovirus reduced Pparg2 messenger RNA levels by 90% and hepatic triglyceride accumulation by 22% compared to the levels in mice injected with an adenoviral empty vector with Western diet feeding...
December 2017: Hepatology Communications
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