MAFA controls genes implicated in insulin biosynthesis and secretion.


AIMS/HYPOTHESIS:Effects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated. MATERIALS AND METHODS:INS-1 stable cell lines permitting inducible up- or downregulation of this transcription factor were established. RESULTS:MAFA overproduction enhanced and its dominant-negative mutant (DN-MAFA) diminished binding of the factor to the insulin promoter, correlating with insulin mRNA levels and cellular protein content. Glucose-stimulated insulin secretion was facilitated by MAFA and blunted by DN-MAFA. This is partly due to alterations in glucokinase production, the glucose sensor of beta cells. In addition, the expression of important beta cell genes, e.g. those encoding solute carrier family 2 (facilitated glucose transporter), member 2 (formerly known as GLUT2), pancreatic and duodenal homeobox factor 1 (PDX1), NK6 transcription factor-related, locus 1 (NKX6-1), glucagon-like peptide 1 receptor (GLP1R), prohormone convertase 1/3 (PCSK1) and pyruvate carboxylase (PC), was regulated positively by MAFA and negatively by DN-MAFA. CONCLUSIONS/INTERPRETATION:The data suggest that MAFA is not only a key activator of insulin transcription, but also a master regulator of genes implicated in maintaining beta cell function, in particular metabolism-secretion coupling, proinsulin processing and GLP1R signalling. Our in vitro study provides molecular targets that explain the phenotype of recently reported Mafa-null mice. We also demonstrate that MAFA is produced specifically in beta cells of human islets. Glucose influenced DNA-binding activity of MAFA in rat islets in a bell-shaped manner. MAFA thus qualifies as a master regulator of beta-cell-specific gene expression and function.






Wang H,Brun T,Kataoka K,Sharma AJ,Wollheim CB




Has Abstract


2007-02-01 00:00:00












  • The effect of improvement in diabetic control on plasma and whole blood viscosity.

    abstract::Rheological studies were made on the blood of 12 diabetic patients after a period of poor diabetic control (HbA1 12.6 +/- 0.7% (mean +/- SD); mean home capillary blood glucose level 11.7 +/- 1.2 mmol/l), and after at least three months of improved control (HbA1 9.1 +/- 0.4%, p < 0.01; mean home capillary blood glucose...


    pub_type: 杂志文章


    authors: Paisey RB,Harkness J,Hartog M,Chadwick T

    更新日期:1980-10-01 00:00:00

  • Is grand multiparity associated with an increased risk of dysglycaemia?

    abstract:AIMS/HYPOTHESIS:We sought to determine the risk of diabetes and IGT/IFG with grand multiparity. SUBJECTS, MATERIALS AND METHODS:Women, aged > or =25 years, from the Australian Diabetes, Obesity and Lifestyle Study and the Crossroads Undiagnosed Disease Study (a rural study in Victoria, Australia), participated in a ho...


    pub_type: 杂志文章


    authors: Simmons D,Shaw J,McKenzie A,Eaton S,Cameron AJ,Zimmet P

    更新日期:2006-07-01 00:00:00

  • The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men.

    abstract:AIMS/HYPOTHESIS:The relationship of androgens to the metabolic syndrome has not been resolved. The polymorphic number of CAG repeats within the androgen receptor gene is inversely associated with the transcriptional activity of target genes. This polymorphism might thus influence testosterone effects on body fat conten...


    pub_type: 杂志文章


    authors: Zitzmann M,Gromoll J,von Eckardstein A,Nieschlag E

    更新日期:2003-01-01 00:00:00

  • A follow-up of 93 newly diagnosed African diabetics for 6 years.

    abstract::In 1971, 107 newly diagnosed black diabetics admitted to Harare Central Hospital, Rhodesia, were studied. Nine died before discharge. In 1977, 93 of the 98 patients discharged alive were traced but of these 38 (41%) had since died. Of 18 autopsies performed the cause of death was hypoglycaemia in 8 patients and hyperg...


    pub_type: 杂志文章


    authors: Castle WM,Wicks AC

    更新日期:1980-01-01 00:00:00

  • Pairing-up SOX to kick-start beta cell genesis.

    abstract::The transcription factor SOX9 is regarded as a crucial player in pancreas development, both maintaining progenitors and later being required for beta cell differentiation. However, very little is known about the possible involvement of other SOX family members in such processes. In this issue, the work of Xu et al (DO...


    pub_type: 评论,杂志文章


    authors: Grapin-Botton A,Seymour PA,Gradwohl G

    更新日期:2015-05-01 00:00:00

  • Reclassification of asymptomatic beta cell autoimmunity: a critical perspective.

    abstract::Type 1 diabetes is an immune-mediated disease leading to almost total beta cell destruction and permanent exogenous insulin dependency. The appearance of clinical symptoms is preceded by an asymptomatic preclinical period, the duration of which is highly individual. The emergence of diabetes-associated autoantibodies ...


    pub_type: 杂志文章


    authors: Knip M,Selvenius J,Siljander H,Veijola R

    更新日期:2017-01-01 00:00:00

  • The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus.

    abstract::Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/l of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose ...


    pub_type: 杂志文章


    authors: Grill V,Cerasi E

    更新日期:1979-01-01 00:00:00

  • An oxidative stress paradox: time for a conceptual change?

    abstract::Oxidative stress has long been considered a key driving factor of many obesity-related health problems. However, recent work by Merry, Tran et al (Diabetologia DOI 10.1007/s00125-016-4084-3 ) challenges this idea with an interesting study using a hepatocyte-specific Gpx1-knockout (HGKO) mouse. GPX1 is an important det...


    pub_type: 评论,社论


    authors: Haas JT,Staels B

    更新日期:2016-12-01 00:00:00

  • High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.

    abstract:AIMS/HYPOTHESIS:In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies. METHODS:A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic flu...


    pub_type: 杂志文章


    authors: Teramo K,Kari MA,Eronen M,Markkanen H,Hiilesmaa V

    更新日期:2004-10-01 00:00:00

  • The metabolic response to hyperglycaemic clamping in insulin-dependent diabetes.

    abstract::The metabolic and hormonal effects of stable hyperglycaemia (10-12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5-6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lac...


    pub_type: 杂志文章


    authors: Nosadini R,Noy GA,Alberti KG,Hodson A,Orskoy H

    更新日期:1981-02-01 00:00:00

  • Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells.

    abstract:AIMS/HYPOTHESIS:Chronic hyperglycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus often leads to a decline in glucose-responsive insulin secretion from pancreatic beta cells, a phenomenon called glucose toxicity. Upon hyperglycaemia, glycation reaction occurs in the beta cells and induces oxidat...


    pub_type: 杂志文章


    authors: Kajimoto Y,Matsuoka T,Kaneto H,Watada H,Fujitani Y,Kishimoto M,Sakamoto K,Matsuhisa M,Kawamori R,Yamasaki Y,Hori M

    更新日期:1999-12-01 00:00:00

  • The effects of insulin and short-term hyperglycaemia on myocardial blood flow in young men with uncomplicated Type I diabetes.

    abstract:AIMS/HYPOTHESIS:Insulin enhances coronary vasodilation in healthy subjects. We tested whether insulin is able to induce coronary vasodilation in Type I (insulin-dependent) diabetic mellitus patients. Additionally, the effect of short-term hyperglycaemia on myocardial perfusion was studied. METHODS:Myocardial blood flo...


    pub_type: 临床试验,杂志文章


    authors: Sundell J,Laine H,Nuutila P,Rönnemaa T,Luotolahti M,Raitakari O,Knuuti J

    更新日期:2002-06-01 00:00:00

  • Assessment of subcutaneous glucose concentration: validation of the wick technique as a reference for implanted electrochemical sensors in normal and diabetic dogs.

    abstract::Employing saline-impregnated cotton threads, an implanted-wick technique was adopted in dogs to obtain specimen from the subcutaneous interstitial compartment in order to estimate its glucose concentration. By measuring the protein, potassium and haemoglobin contents, the centrifuged wick fluid was shown to contain th...


    pub_type: 杂志文章


    authors: Fischer U,Ertle R,Abel P,Rebrin K,Brunstein E,Hahn von Dorsche H,Freyse EJ

    更新日期:1987-12-01 00:00:00

  • Ultrastructure of heart muscle in short-term diabetic rats: influence of insulin treatment.

    abstract::The ultrastructure of myocardium was examined in short-term diabetic rats. Morphometric analysis showed the volume of myocytic mitochondria, sarcoplasmic reticulum and lipid droplets to be significantly increased compared with those of control animals. Further measurements of mitochondria and sarcoplasmic reticulum in...


    pub_type: 杂志文章


    authors: Reinilä A,Akerblom HK

    更新日期:1984-09-01 00:00:00

  • Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

    abstract:AIMS/HYPOTHESIS:Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased...


    pub_type: 杂志文章


    authors: Christiansen MS,Hommel E,Magid E,Feldt-Rasmussen B

    更新日期:2002-01-01 00:00:00

  • Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro.

    abstract::The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon ...


    pub_type: 杂志文章


    authors: Boillot D,in't Veld P,Sai P,Feutren G,Gepts W,Assan R

    更新日期:1985-06-01 00:00:00

  • Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes.

    abstract:AIMS/HYPOTHESIS:We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat r...


    pub_type: 杂志文章


    authors: West SG,Hecker KD,Mustad VA,Nicholson S,Schoemer SL,Wagner P,Hinderliter AL,Ulbrecht J,Ruey P,Kris-Etherton PM

    更新日期:2005-01-01 00:00:00

  • Effect of past and concurrent body mass index on prevalence of glucose intolerance and type 2 (non-insulin-dependent) diabetes and on insulin response. The Israel study of glucose intolerance, obesity and hypertension.

    abstract::A representative sample (n = 2140) of the Israeli Jewish population aged 40-70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past bo...


    pub_type: 杂志文章


    authors: Modan M,Karasik A,Halkin H,Fuchs Z,Lusky A,Shitrit A,Modan B

    更新日期:1986-02-01 00:00:00

  • Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft.

    abstract::Islet allografts in insulin-dependent diabetic (IDDM) patients exhibit variable survival lengths and low rates of insulin-independence despite treatment with anti-T-cell antibodies and maintenance immunosuppression. Use of poorly characterized freshly isolated preparations makes it difficult to determine whether failu...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Keymeulen B,Ling Z,Gorus FK,Delvaux G,Bouwens L,Grupping A,Hendrieckx C,Pipeleers-Marichal M,Van Schravendijk C,Salmela K,Pipeleers DG

    更新日期:1998-04-01 00:00:00

  • The clinical application of genetic testing in type 2 diabetes: a patient and physician survey.

    abstract:AIMS/HYPOTHESIS:Advances in type 2 diabetes genetics have raised hopes that genetic testing will improve disease prediction, prevention and treatment. Little is known about current physician and patient views regarding type 2 diabetes genetic testing. We hypothesised that physician and patient views would differ regard...


    pub_type: 杂志文章


    authors: Grant RW,Hivert M,Pandiscio JC,Florez JC,Nathan DM,Meigs JB

    更新日期:2009-11-01 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...


    pub_type: 杂志文章


    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

  • Identification of IL-1beta-induced messenger RNAs in rat pancreatic beta cells by differential display of messenger RNA.

    abstract:AIMS/HYPOTHESIS:Interleukin-1beta is a putative mediator of pancreatic beta-cell dysfunction and damage in Type I (insulin-dependent) diabetes mellitus. To better understand the molecular mechanisms involved in IL-1beta effects, we carried out a differential display of mRNA by RT-PCR to identify novel cytokine-regulate...


    pub_type: 杂志文章


    authors: Chen MC,Schuit F,Eizirik DL

    更新日期:1999-10-01 00:00:00

  • Neuronal control of peripheral nutrient partitioning.

    abstract::The appropriate utilisation, storage and conversion of nutrients in peripheral tissues, referred to as nutrient partitioning, is a fundamental process to adapt to nutritional and metabolic challenges and is thus critical for the maintenance of a healthy energy balance. Alterations in this process during nutrient exces...


    pub_type: 杂志文章,评审


    authors: Manceau R,Majeur D,Alquier T

    更新日期:2020-04-01 00:00:00

  • Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog.

    abstract::Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ i...


    pub_type: 杂志文章


    authors: Koffler M,Imamura T,Santeusanio F,Helderman JH

    更新日期:1988-04-01 00:00:00

  • Properties of isolated human islets of Langerhans: insulin secretion, glucose oxidation and protein phosphorylation.

    abstract::In the present study, human islets were isolated by collagenase digestion from the pancreases of three kidney donors. Maintainance of the islets in tissue culture enabled insulin release, glucose oxidation and Ca2+ -calmodulin-dependent protein phosphorylation to be determined using the same islets. Increasing glucose...


    pub_type: 杂志文章


    authors: Harrison DE,Christie MR,Gray DW

    更新日期:1985-02-01 00:00:00

  • Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats.

    abstract:AIMS/HYPOTHESIS:Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available. METHODS:We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneou...


    pub_type: 杂志文章


    authors: Medina A,Parween S,Ullsten S,Vishnu N,Siu YT,Quach M,Bennet H,Balhuizen A,Åkesson L,Wierup N,Carlsson PO,Ahlgren U,Lernmark Å,Fex M

    更新日期:2018-04-01 00:00:00

  • Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids.

    abstract:AIMS/HYPOTHESIS:According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as i...


    pub_type: 杂志文章,多中心研究


    authors: Rump P,Popp-Snijders C,Heine RJ,Hornstra G

    更新日期:2002-03-01 00:00:00

  • No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort.

    abstract:AIMS/HYPOTHESIS:Although the variable number tandem repeat (VNTR) minisatellite 5' to the insulin gene is among the most studied polymorphisms in diabetes, the relationships between VNTR variation, diabetes-related traits and predisposition to type 2 diabetes remain unclear. Since inadequate sample size is likely to ha...


    pub_type: 杂志文章,多中心研究


    authors: Bennett A,Sovio U,Ruokonen A,Martikainen H,Pouta A,Taponen S,Hartikainen AL,Franks S,Peltonen L,Elliott P,Järvelin MR,McCarthy MI

    更新日期:2005-05-01 00:00:00

  • A prospective study of the effect of 12 months treatment on serum lipids and apolipoproteins A-I and B in Type 2 (non-insulin-dependent) diabetes.

    abstract::Serum high density lipoprotein cholesterol, total cholesterol, triglyceride and apolipoproteins A-I and B were studied at diagnosis and after 12 months conventional treatment in a group of Type 2 (non-insulin-dependent) diabetic patients. No significant deleterious effect on serum lipids and apolipoproteins was seen i...


    pub_type: 杂志文章


    authors: Taylor KG,John WG,Matthews KA,Wright AD

    更新日期:1982-12-01 00:00:00

  • Phosphoenolpyruvate in rat pancreatic islets: a possible intracellular trigger of insulin release?

    abstract::The content of phosphoenolpyruvate (PEP) has been measured in isolated rat islets of Langerhans incubated in vitro. Islet PEP was higher in islets incubated with 16.7 mmol/1 glucose than in islets incubated with zero or 2.8 mmol/1 glucose. Islet PEP content was also increased in islet incubated with 5 mmol/1 D-glycera...


    pub_type: 杂志文章


    authors: Sugden MC,Ashcroft SJ

    更新日期:1977-09-01 00:00:00