当前位置： SCI文献检索 > DIABETOLOGIA期刊下所有文献 > Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism.

Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism.

Abstract：

AIMS/HYPOTHESIS:The mechanisms by which transcription factor 7-like 2 (TCF7L2) regulates the pathways that are important in the pathogenesis of type 2 diabetes are unknown. We therefore examined the role of TCF7L2 in hepatic glucose production (HGP) in vitro and characterised the whole-genome chromatin occupancy of TCF7L2 in hepatocytes. METHODS:We investigated the effect of TCF7L2 silencing and overexpression on HGP from gluconeogenic precursors and used chromatin-immunoprecipitation (ChIP) combined with massively parallel DNA sequencing (ChIP-Seq) to investigate the DNA binding patterns of TCF7L2 across the whole genome. RESULTS:Silencing of TCF7L2 induced a marked increase in basal HGP, which was accompanied by significant increases in the expression of the gluconeogenic genes Fbp1, Pck1 and G6pc. Overexpression of Tcf7l2 reversed this phenotype and significantly reduced HGP. TCF7L2 silencing did not affect the half-maximal inhibitory concentration of insulin or metformin, but HGP remained elevated in TCF7L2-silenced cells due to the increased baseline HGP. Using ChIP-Seq, we detected 2,119 binding events across the genome. Pathway analysis demonstrated that diabetes genes were significantly over-represented in the dataset. Our results indicate that TCF7L2 binds directly to multiple genes that are important in regulation of glucose metabolism in the liver, including Pck1, Fbp1, Irs1, Irs2, Akt2, Adipor1, Pdk4 and Cpt1a. CONCLUSIONS/INTERPRETATION:TCF7L2 is an important regulator of HGP in vitro and binds directly to genes that are important in pathways of glucose metabolism in the liver. These data highlight the possibility that TCF7L2 may affect fasting and postprandial hyperglycaemia in carriers of at-risk TCF7L2 genetic polymorphisms.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Norton L,Fourcaudot M,Abdul-Ghani MA,Winnier D,Mehta FF,Jenkinson CP,Defronzo RA

doi

10.1007/s00125-011-2289-z

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

3132-42

issue

12

eissn

0012-186X

issn

1432-0428

journal_volume

54

pub_type

杂志文章

相关文献

DIABETOLOGIA文献大全
  • Long-term suppression of postprandial hyperglycaemia with acarbose retards the development of neuropathies in the BB/W-rat.

    abstract：:The effect of the alpha-glucosidase inhibitor acarbose on postprandial hyperglycaemia was explored in the spontaneously diabetic BB/W-rat. Acarbose-treatment (5 mg.kg body weight-1.day-1) of diabetic BB/W-rats maintained on small doses of insulin, was associated with a 40% reduction in the 24-h glucose area compared t...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00401199

    authors： Sima AA,Chakrabarti S

    更新日期：1992-04-01 00:00:00

  • A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro.

    abstract：:Cyclic adenosine 5'diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2+. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s001250051026

    authors： Yagui K,Shimada F,Mimura M,Hashimoto N,Suzuki Y,Tokuyama Y,Nata K,Tohgo A,Ikehata F,Takasawa S,Okamoto H,Makino H,Saito Y,Kanatsuka A

    更新日期：1998-09-01 00:00:00

  • The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men.

    abstract：AIMS/HYPOTHESIS:Glucagon-like peptide-1 (GLP-1), a polypeptide hormone secreted by the l-cells in the gastrointestinal tract, has shown promising effects as a new treatment modality for patients with Type II (non-insulin-dependent) diabetes mellitus. However, the pharmacokinetic profile of native GLP-1 with a rapid eli...

    journal_title：Diabetologia

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1007/s00125-001-0719-z

    authors： Agersø H,Jensen LB,Elbrønd B,Rolan P,Zdravkovic M

    更新日期：2002-02-01 00:00:00

  • A common mitochondrial DNA variant is associated with insulin resistance in adult life.

    abstract：:Mitochondrial DNA is maternally inherited. Mitochondrial DNA mutations could contribute to the excess of maternal over paternal inheritance of non-insulin-dependent diabetes mellitus (NIDDM). We therefore investigated the relationship between this variant, insulin resistance and other risk factors in a cohort which ha...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s001250050866

    authors： Poulton J,Brown MS,Cooper A,Marchington DR,Phillips DI

    更新日期：1998-01-01 00:00:00

  • Transition of metabolic phenotypes and risk of subclinical atherosclerosis according to BMI: a prospective study.

    abstract：AIMS/HYPOTHESIS:The cardiometabolic risk associated with metabolically healthy obesity (MHO) remains the subject of debate. It is unclear whether MHO is a transient condition that affects subclinical atherosclerosis risk. In this study, we aimed to investigate the association of MHO and its transition over time with in...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-020-05116-5

    authors： Lin L,Zhang J,Jiang L,Du R,Hu C,Lu J,Wang T,Li M,Zhao Z,Xu Y,Xu M,Bi Y,Ning G,Wang W,Chen Y

    更新日期：2020-07-01 00:00:00

  • Pentamidine, a new diabetogenic drug in laboratory rodents.

    abstract：:The antiprotozoal drug, pentamidine, has been reported to induce hypoglycaemia associated with inappropriately high plasma insulin concentrations, followed by insulin-dependent diabetes mellitus. It has been suggested that this drug can be toxic to the islet B cell, inducing early cytolytic release of insulin leading ...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00282521

    authors： Saï P,Boillot D,Boitard C,Debray-Sachs M,Reach G,Assan R

    更新日期：1983-11-01 00:00:00

  • Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction.

    abstract：:Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GDM) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes. It has been hypothesised that epigene...

    journal_title：Diabetologia

    pub_type： 杂志文章,评审

    doi：10.1007/s00125-019-05011-8

    authors： Elliott HR,Sharp GC,Relton CL,Lawlor DA

    更新日期：2019-12-01 00:00:00

  • Lack of acute effect of amylin (islet associated polypeptide) on insulin sensitivity during hyperinsulinaemic euglycaemic clamp in humans.

    abstract：:It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeo...

    journal_title：Diabetologia

    pub_type： 临床试验,杂志文章

    doi：10.1007/s001250050088

    authors： Wilding JP,Khandan-Nia N,Bennet WM,Gilbey SG,Beacham J,Ghatei MA,Bloom SR

    更新日期：1994-02-01 00:00:00

  • Paradoxical glucagon response after stimulation with glucose and arginine in isolated pancreatic sand rat islets.

    abstract：:Isolated pancreatic islets of normoglycemic sand rats do not respond to 2.5 mM glucose with an enhanced glucagon secretion, which could be observed in normal Wistar rats. Arginine stimulates glucagon release in the presence of 2.5 mM glucose in Wistar rats as well as in sand rats. The secretion pattern is not caused b...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00422820

    authors： Ziegler M,Hahn HJ,Ziegler B,Köhler E,Fiedler H

    更新日期：1975-02-01 00:00:00

  • Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine.

    abstract：:N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor alpha (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velo...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00418340

    authors： Sagara M,Satoh J,Wada R,Yagihashi S,Takahashi K,Fukuzawa M,Muto G,Muto Y,Toyota T

    更新日期：1996-03-01 00:00:00

  • HGF/NK4 inhibited VEGF-induced angiogenesis in in vitro cultured endothelial cells and in vivo rabbit model.

    abstract：AIMS/HYPOTHESIS:As vascular endothelial growth factor (VEGF) plays a pivotal role in the development of diabetic retinopathy, inhibition of angiogenesis induced by VEGF is crucial to treat diabetic retinopathy. HGF (hepatocyte growth factor)/NK4, containing the N-terminal hairpin domain and the four subsequent kringle ...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-002-0954-y

    authors： Nakabayashi M,Morishita R,Nakagami H,Kuba K,Matsumoto K,Nakamura T,Tano Y,Kaneda Y

    更新日期：2003-01-01 00:00:00

  • G protein-coupled receptors as new therapeutic targets for type 2 diabetes.

    abstract：:G protein-coupled receptors (GPCRs) in the gut-brain-pancreatic axis are key players in the postprandial control of metabolism and food intake. A number of intestinally located receptors have been implicated in the chemo-detection of ingested nutrients, and in the pancreatic islets and nervous system GPCRs play essent...

    journal_title：Diabetologia

    pub_type： 杂志文章,评审

    doi：10.1007/s00125-015-3825-z

    authors： Reimann F,Gribble FM

    更新日期：2016-02-01 00:00:00

  • Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe.

    abstract：AIMS/HYPOTHESIS:Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-017-4353-9

    authors： Egan AM,Vellinga A,Harreiter J,Simmons D,Desoye G,Corcoy R,Adelantado JM,Devlieger R,Van Assche A,Galjaard S,Damm P,Mathiesen ER,Jensen DM,Andersen L,Lapolla A,Dalfrà MG,Bertolotto A,Mantaj U,Wender-Ozegowska E,Zawi

    更新日期：2017-10-01 00:00:00

  • Insulin receptor tyrosine-kinase activity is altered in both muscle and adipose tissue from non-obese normoglycaemic insulin-resistant subjects.

    abstract：:We performed i.v. insulin tolerance test in 30 non-obese (BMI < 30 male and < 28 female) non-diabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (K(itt) values). Then we compared the tyrosine-kinase activity of immunopurif...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF02369353

    authors： Grasso G,Frittitta L,Anello M,Russo P,Sesti G,Trischitta V

    更新日期：1995-01-01 00:00:00

  • Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients.

    abstract：:The intraperitoneal route may offer more physiological insulin delivery through absorption of a proportion of the dose into the portal circulation. We have compared 1-h square-wave and bolus supplemental infusions of a fixed dose of 10 U of intraperitoneal insulin in 6 C-peptide negative insulin-dependent diabetic pat...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00265019

    authors： Jimenez JT,Walford S,Home PD,Hanning I,Alberti KG

    更新日期：1985-10-01 00:00:00

  • Chronic muscle stimulation improves insulin sensitivity while increasing subcellular lipid droplets and reducing selected diacylglycerol and ceramide species in obese Zucker rats.

    abstract：AIMS/HYPOTHESIS:Although insulin resistance has been associated with accumulations of specific intramuscular fatty acids and altered subcellular localisation of lipid droplets, these concepts remain controversial. Therefore, we aimed to identify specific intramuscular fatty acids and subcellular lipid localisations ass...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-014-3169-0

    authors： Holloway GP,Han XX,Jain SS,Bonen A,Chabowski A

    更新日期：2014-04-01 00:00:00

  • Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.

    abstract：AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. METHODS:In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing allele...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-014-3308-7

    authors： Zhu J,Zong G,Lu L,Gan W,Ji L,Hu R,Ye X,Sun L,Loos RJ,Li H,Lin X

    更新日期：2014-09-01 00:00:00

  • A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes.

    abstract：AIMS/HYPOTHESIS:This 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients. METHODS:Insulin-naive adults (n=582, HbA(1c) 7.5-1...

    journal_title：Diabetologia

    pub_type： 杂志文章,多中心研究,随机对照试验

    doi：10.1007/s00125-007-0911-x

    authors： Rosenstock J,Davies M,Home PD,Larsen J,Koenen C,Schernthaner G

    更新日期：2008-03-01 00:00:00

  • Imprecision of new criteria for the oral glucose tolerance test.

    abstract：:Subjects selected from a centre specializing in diabetes detection have been classified using nine different methods of diagnosis including the recent criteria of the National Diabetes Data Group and the World Health Organization. The applicability of these two new criteria have been evaluated and compared with seven ...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00297390

    authors： Massari V,Eschwège E,Valleron AJ

    更新日期：1983-02-01 00:00:00

  • Assessment of the new criteria for diabetes mellitus according to 10-year relative survival rates.

    abstract：:The validity of the new diagnostic criteria for diabetes mellitus for Japanese subjects was assessed by the long-term prognosis of 501 patients, found in an epidemiological survey of 6,681 people in a Japanese town. Ten-year relative survival rates were examined in relation to the 50 g oral glucose tolerance test (ser...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00252627

    authors： Sasaki A

    更新日期：1981-03-01 00:00:00

  • Influence of protamine on adhesion, chemotaxis and proliferation of human vascular smooth muscle cells.

    abstract：:It has been shown that, in streptozotocin diabetic rats, protamine-retarded insulin administered in vivo stimulates intimal hyperplasia in balloon-injured carotid artery. The aim of this study was to evaluate the influence of protamine on cultured human vascular smooth muscle cells (h VSMC), by observing its effects o...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s001250050644

    authors： Cavalot F,Russo I,Mattiello L,Anfossi G,Massucco P,Mularoni E,Hahn AW,Trovati M

    更新日期：1997-01-01 00:00:00

  • In vitro kinetics of insulin release by microencapsulated rat islets: effect of the size of the microcapsules.

    abstract：:Microencapsulation has been proposed to protect islets of Langerhans against immune rejection in xenogenic transplantation. However, to achieve glucose homeostasis in human diabetic patients, insulin release by microencapsulated islets must increase in response to a glucose load. We microencapsulated isolated rat isle...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/BF00279134

    authors： Chicheportiche D,Reach G

    更新日期：1988-01-01 00:00:00

  • Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes.

    abstract：AIMS/HYPOTHESIS:Insulin-like growth factor-1 is a major childhood growth factor and promotes pancreatic islet cell survival and growth in vitro. We hypothesised that genetic variation in IGF1 might be associated with childhood growth, glucose metabolism and type 1 diabetes risk. We therefore examined the association be...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-008-0970-7

    authors： Vella A,Bouatia-Naji N,Heude B,Cooper JD,Lowe CE,Petry C,Ring SM,Dunger DB,Todd JA,Ong KK

    更新日期：2008-05-01 00:00:00

  • A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.

    abstract：AIMS/HYPOTHESIS:The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical....

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-008-1191-9

    authors： Fex M,Haemmerle G,Wierup N,Dekker-Nitert M,Rehn M,Ristow M,Zechner R,Sundler F,Holm C,Eliasson L,Mulder H

    更新日期：2009-02-01 00:00:00

  • Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study.

    abstract：AIMS/HYPOTHESIS:We determined the effects of 6 years of lifestyle intervention in persons with impaired glucose tolerance (IGT) on the development of retinopathy, nephropathy and neuropathy over a 20 year period. METHODS:In 1986, 577 adults with IGT from 33 clinics in Da Qing, China were randomly assigned by clinic to...

    journal_title：Diabetologia

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s00125-010-1948-9

    authors： Gong Q,Gregg EW,Wang J,An Y,Zhang P,Yang W,Li H,Li H,Jiang Y,Shuai Y,Zhang B,Zhang J,Gerzoff RB,Roglic G,Hu Y,Li G,Bennett PH

    更新日期：2011-02-01 00:00:00

  • Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice.

    abstract：AIMS/HYPOTHESIS:Endothelial-endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-017-4243-1

    authors： Staels W,Heremans Y,Leuckx G,Van Gassen N,Salinno C,De Groef S,Cools M,Keshet E,Dor Y,Heimberg H,De Leu N

    更新日期：2017-06-01 00:00:00

  • A genetic variant of G6PC2 is associated with type 2 diabetes and fasting plasma glucose level in the Chinese population.

    abstract：AIMS/HYPOTHESIS:Single nucleotide polymorphisms (SNPs) in G6PC2 have been reported to be associated with fasting plasma glucose level in several populations of European descent. However, whether G6PC2 variants have a similar effect in other ethnic groups is unknown. The aim of this study was to investigate the effect o...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-008-1241-3

    authors： Hu C,Zhang R,Wang C,Ma X,Wang C,Fang Q,Bao Y,Xiang K,Jia W

    更新日期：2009-03-01 00:00:00

  • Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells.

    abstract：AIMS/HYPOTHESIS:Glucose and the peptide growth factors insulin, IGF-I and IGF-II strongly regulate beta cell mass. Furthermore, beta cell expression of IGF-I receptor (Igf1r) and insulin receptor (Insr) is mandatory for several steps of insulin secretion. MATERIALS AND METHODS:We hypothesised that glucose concentratio...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s00125-005-1860-x

    authors： Raile K,Klammt J,Laue S,Garten A,Blüher M,Kralisch S,Klöting N,Kiess W

    更新日期：2005-09-01 00:00:00

  • Purchase of antidepressant agents by patients with type 1 diabetes is associated with increased mortality rates in women but not in men.

    abstract：AIMS/HYPOTHESIS:Individuals with diabetes have increased mortality rates compared with the general population. In patients with type 2 diabetes depression further contributes to the increased mortality. Depression and mortality rates in patients with type 1 diabetes are an understudied phenomenon. We therefore studied ...

    journal_title：Diabetologia

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s00125-011-2347-6

    authors： Ahola AJ,Harjutsalo V,Saraheimo M,Forsblom C,Groop PH,FinnDiane Study Group.

    更新日期：2012-01-01 00:00:00

  • Basal activity profiles of NPH and [Nepsilon-palmitoyl Lys (B29)] human insulins in subjects with IDDM.

    abstract：:[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed fol...

    journal_title：Diabetologia

    pub_type： 杂志文章

    doi：10.1007/s001250050876

    authors： Radziuk J,Pye S,Bradley B,Braaten J,Vignati L,Roach P,Bowsher R,DiMarchi R,Chance R

    更新日期：1998-01-01 00:00:00