Mutation at position -132 in the islet amyloid polypeptide ( IAPP) gene promoter enhances basal transcriptional activity through a new CRE-like binding site.

Abstract:

AIMS/HYPOTHESIS:Mutations in the islet amyloid polypeptide ( IAPP) gene may play a potential role in the abnormal regulation or expression of the peptide. The aim of this study was to determine the functional role of the -132 G/A mutation reported in the promoter region of the IAPP gene in a population of Spanish Type 2 diabetic patients. METHODS:We investigated the transcriptional activity using MIN6 cells and luciferase reporter plasmids in several culture conditions. Key regulatory elements of the IAPP promoter region were also analysed by electrophoretic mobility shift assays (EMSA). RESULTS:The mutant construct doubled IAPP transcriptional activity ( p<0.001). Both constructs showed severely reduced promoter activity (four-fold decrease) in the presence of verapamil and diazoxide. In contrast, IAPP promoter activity was doubled after incubation with forskolin or dexamethasone, regardless of the glucose concentrations in the culture media. EMSA revealed that the -132 G/A mutation increased the binding affinity through two DNA-protein complexes. In addition, a cAMP-responsive element binding protein (CREB) was identified by super-shift EMSA. CONCLUSIONS/INTERPRETATION:Our studies show that the wild-type and the mutant constructs are regulated in a similar pattern under all conditions, strongly indicating that the -132 G/A mutation increases basal but not inducible transcription. These results may be explained by new binding to the mutant region through CREB and other transcription factors not yet identified.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Novials A,Mato E,Lucas M,Franco C,Rivas M,Santisteban P,Gomis R

doi

10.1007/s00125-004-1439-y

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

1167-1174

issue

7

eissn

0012-186X

issn

1432-0428

pii

10.1007/s00125-004-1439-y

journal_volume

47

pub_type

杂志文章
  • Stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis activation induces intra-islet glucagon-like peptide-1 (GLP-1) production and enhances beta cell survival.

    abstract:AIMS/HYPOTHESIS:The endogenous production of stromal cell-derived factor-1 (SDF-1) in beta cells in transgenic mice attenuates the development of diabetes in response to streptozotocin. Here we propose that beta cell injury induces SDF-1 production, and the SDF-1/chemokine (C-X-C motif) receptor 4 (CXCR4) interaction a...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-011-2181-x

    authors: Liu Z,Stanojevic V,Avadhani S,Yano T,Habener JF

    更新日期:2011-08-01 00:00:00

  • Repurposing metformin for the prevention of cancer and cancer recurrence.

    abstract::Multiple epidemiological studies have documented an association between metformin, used for treatment of type 2 diabetes, and reduced cancer incidence and mortality. Cell line models may not accurately reflect the effects of metformin in the clinical setting. Moreover, findings from animal model studies have been inco...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-017-4372-6

    authors: Heckman-Stoddard BM,DeCensi A,Sahasrabuddhe VV,Ford LG

    更新日期:2017-09-01 00:00:00

  • Molecular and functional profiling of human islets: from heterogeneity to human phenotypes.

    abstract::Efforts to phenotype pancreatic islets have contributed tremendously to our present understanding of endocrine function and diabetes. A continued evolution in approaches to study islet physiology is important given the need to establish reference points for mature islet functionality, understanding biological variatio...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-020-05159-8

    authors: Arrojo E Drigo R,Roy B,MacDonald PE

    更新日期:2020-10-01 00:00:00

  • Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes.

    abstract:AIMS/HYPOTHESIS:Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesis...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-017-4214-6

    authors: Abdelsaid M,Coucha M,Hafez S,Yasir A,Johnson MH,Ergul A

    更新日期:2017-04-01 00:00:00

  • Anti-GAD antibodies in Chinese patients with youth and adult-onset IDDM and NIDDM.

    abstract::An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies - islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diab...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250050845

    authors: Thai AC,Ng WY,Loke KY,Lee WR,Lui KF,Cheah JS

    更新日期:1997-12-01 00:00:00

  • Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium.

    abstract::To determine whether increased oxidative stress in diabetes mellitus is due to an impaired free-radical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00398053

    authors: Kashiwagi A,Asahina T,Ikebuchi M,Tanaka Y,Takagi Y,Nishio Y,Kikkawa R,Shigeta Y

    更新日期:1994-03-01 00:00:00

  • Non-neural tyrosine hydroxylase, via modulation of endocrine pancreatic precursors, is required for normal development of beta cells in the mouse pancreas.

    abstract:AIMS/HYPOTHESIS:Apart from transcription factors, little is known about the molecules that modulate the proliferation and differentiation of pancreatic endocrine cells. The early expression of tyrosine hydroxylase (TH) in a subset of glucagon(+) cells led us to investigate whether catecholamines have a role in beta cel...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-014-3341-6

    authors: Vázquez P,Robles AM,de Pablo F,Hernández-Sánchez C

    更新日期:2014-11-01 00:00:00

  • Raised serum apolipoprotein (a) in active diabetic retinopathy.

    abstract::Progressive capillary occlusion often leads to severe retinopathy within 15-20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein(a), a complex formed by apolipoprotein(a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It m...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00399100

    authors: Maioli M,Tonolo G,Pacifico A,Ciccarese M,Brizzi P,Kohner EM,Porta M

    更新日期:1993-01-01 00:00:00

  • The effect of insulin on renal sodium metabolism. A review with clinical implications.

    abstract::Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/BF00252649

    authors: DeFronzo RA

    更新日期:1981-09-01 00:00:00

  • Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits.

    abstract:AIMS/HYPOTHESIS:Empagliflozin (EMPA), an inhibitor of the renal sodium-glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na+ ([Na+]c) and Ca2+ ([Ca2+]c) concentrations and decreased ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-016-4134-x

    authors: Baartscheer A,Schumacher CA,Wüst RC,Fiolet JW,Stienen GJ,Coronel R,Zuurbier CJ

    更新日期:2017-03-01 00:00:00

  • Cardiovascular risk assessment scores for people with diabetes: a systematic review.

    abstract::People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a ge...

    journal_title:Diabetologia

    pub_type: 杂志文章,评审

    doi:10.1007/s00125-009-1454-0

    authors: Chamnan P,Simmons RK,Sharp SJ,Griffin SJ,Wareham NJ

    更新日期:2009-10-01 00:00:00

  • The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis.

    abstract:AIMS/HYPOTHESIS:Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components. METHODS:Incident diabetes was assessed ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-016-4003-7

    authors: Joseph JJ,Echouffo-Tcheugui JB,Carnethon MR,Bertoni AG,Shay CM,Ahmed HM,Blumenthal RS,Cushman M,Golden SH

    更新日期:2016-09-01 00:00:00

  • A genome-wide association scan for acute insulin response to glucose in Hispanic-Americans: the Insulin Resistance Atherosclerosis Family Study (IRAS FS).

    abstract:AIMS/HYPOTHESIS:This study sought to identify genes and regions in the human genome that are associated with the acute insulin response to glucose (AIRg), an important predictor of type 2 diabetes, in Hispanic-American participants from the Insulin Resistance Atherosclerosis Family Study (IRAS FS). METHODS:A two-stage...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-009-1373-0

    authors: Rich SS,Goodarzi MO,Palmer ND,Langefeld CD,Ziegler J,Haffner SM,Bryer-Ash M,Norris JM,Taylor KD,Haritunians T,Rotter JI,Chen YD,Wagenknecht LE,Bowden DW,Bergman RN

    更新日期:2009-07-01 00:00:00

  • Metabolic syndrome and coronary heart disease in South Asians, African-Caribbeans and white Europeans: a UK population-based cross-sectional study.

    abstract:AIMS/HYPOTHESIS:The aim of this study was to study differences in the prevalence of the metabolic syndrome and its associations with prevalent CHD according to ethnicity and sex. METHODS:We performed a combined analysis of two population-based cross-sectional studies conducted between 1988 and 1991 that followed ident...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-005-1689-3

    authors: Tillin T,Forouhi N,Johnston DG,McKeigue PM,Chaturvedi N,Godsland IF

    更新日期:2005-04-01 00:00:00

  • Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease.

    abstract::Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) an...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00410287

    authors: Hitman GA,Hawrami K,McCarthy MI,Viswanathan M,Snehalatha C,Ramachandran A,Tuomilehto J,Tuomilehto-Wolf E,Nissinen A,Pedersen O

    更新日期:1995-04-01 00:00:00

  • A population-based prevalence survey of known diabetes mellitus in northern Italy based upon multiple independent sources of ascertainment.

    abstract::The aims of this survey were (1) to estimate the prevalence of known diabetes mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different data sources available in Italy; (3) to identify a population-based cohort of diabetic patients. Multiple independent data sources were used and the capture-re...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00399931

    authors: Bruno G,Bargero G,Vuolo A,Pisu E,Pagano G

    更新日期:1992-09-01 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...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-009-1512-7

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

    更新日期:2009-11-01 00:00:00

  • Immunoradiometric assay of insulin, intact proinsulin and 32-33 split proinsulin and radioimmunoassay of insulin in diet-treated type 2 (non-insulin-dependent) diabetic subjects.

    abstract::Plasma insulin, intact proinsulin and 32-33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabe...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF02342446

    authors: Clark PM,Levy JC,Cox L,Burnett M,Turner RC,Hales CN

    更新日期:1992-05-01 00:00:00

  • Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes.

    abstract:AIMS/HYPOTHESIS:Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T c...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-014-3262-4

    authors: Favaro E,Carpanetto A,Lamorte S,Fusco A,Caorsi C,Deregibus MC,Bruno S,Amoroso A,Giovarelli M,Porta M,Perin PC,Tetta C,Camussi G,Zanone MM

    更新日期:2014-08-01 00:00:00

  • Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice.

    abstract:AIMS/HYPOTHESIS:Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the pr...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-012-2578-1

    authors: Kuwabara T,Mori K,Mukoyama M,Kasahara M,Yokoi H,Saito Y,Ogawa Y,Imamaki H,Kawanishi T,Ishii A,Koga K,Mori KP,Kato Y,Sugawara A,Nakao K

    更新日期:2012-08-01 00:00:00

  • Insulin binding and insulin action in rat fat cells after adrenalectomy.

    abstract::Insulin binding and the effect of insulin on the transport of 3-O-methylglucose, lipogenesis from glucose, glucose oxidation and lipolysis was studied in fat cells of adrenalectomised rats and of a control group of sham-operated rats. The serum insulin level of the adrenalectomised rats (0.7 ng/ml) was lower than that...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00280524

    authors: Häring H,Calle C,Bug A,Renner R,Hepp KD,Kemmler W

    更新日期:1980-10-01 00:00:00

  • Pre-diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells.

    abstract::Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on va...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00280892

    authors: Dean BM,Walker R,Bone AJ,Baird JD,Cooke A

    更新日期:1985-07-01 00:00:00

  • Secular trend for mortality from breast cancer and the association between diabetes and breast cancer in Taiwan between 1995 and 2006.

    abstract:AIMS/HYPOTHESIS:Studies have identified an association between diabetes and breast cancer in postmenopausal women in Western countries. Such an association needs to be confirmed in an Asian population. The aim of this study was to evaluate the secular trend for breast cancer mortality in Taiwanese women in the general ...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-008-1204-8

    authors: Tseng CH,Chong CK,Tai TY

    更新日期:2009-02-01 00:00:00

  • Exendin-4 increases histone acetylase activity and reverses epigenetic modifications that silence Pdx1 in the intrauterine growth retarded rat.

    abstract:AIMS/HYPOTHESIS:The abnormal intrauterine milieu of intrauterine growth retardation (IUGR) permanently alters gene expression and function of pancreatic beta cells leading to the development of diabetes in adulthood. Expression of the pancreatic homeobox transcription factor Pdx1 is permanently reduced in IUGR islets s...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-011-2250-1

    authors: Pinney SE,Jaeckle Santos LJ,Han Y,Stoffers DA,Simmons RA

    更新日期:2011-10-01 00:00:00

  • IGF-1 and cardiometabolic diseases: a Mendelian randomisation study.

    abstract:AIMS/HYPOTHESIS:Abnormal serum IGF-1 levels are associated with an increased risk of type 2 diabetes and cardiovascular disease. However, the causal role of IGF-1 levels within the normal range in cardiometabolic disease remains unclear. We employed Mendelian randomisation to explore the associations between geneticall...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s00125-020-05190-9

    authors: Larsson SC,Michaëlsson K,Burgess S

    更新日期:2020-09-01 00:00:00

  • Markers of renal tubular dysfunction measured annually do not predict risk of microalbuminuria in the first few years after diagnosis of Type I diabetes.

    abstract:AIMS/HYPOTHESIS:Early detection of risk of microalbuminuria could prevent early renal damage. We investigated whether urine retinol binding protein and N-acetyl-glucosaminidase could predict the risk of microalbuminuria in a large cohort of children followed from diagnosis of Type I (insulin-dependent) diabetes mellitu...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/s001250051603

    authors: Schultz CJ,Dalton RN,Neil HA,Konopelska-Bahu T,Dunger DB,Oxford Regional Prospective Study Group.

    更新日期:2001-02-01 00:00:00

  • Prevalence of diabetes mellitus in north-western Tanzania.

    abstract::The prevalence of diabetes mellitus in 3,145 Tanzanian Africans living in three different areas of the country was studied. Fasting capillary blood glucose concentrations were measured by Dextrometer and if the levels were greater than or equal to 5.5 mmol/l an oral glucose tolerance test was performed. When using the...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00266032

    authors: Ahrén B,Corrigan CB

    更新日期:1984-05-01 00:00:00

  • Effects of insulin on the disposal of 14C-labelled very low density lipoprotein triglycerides in intact and hepatectomized rats.

    abstract::In sham-operated rats, intravenous administration of 14C-very low density lipoprotein triglycerides (with labelled esterified fatty acids) caused an initial decrease and subsequent increase in plasma 14C-lipids of both very low density lipoproteins (VLDL) (density less than 1.006) and lipoproteins of density greater t...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00282718

    authors: Argilés J,Herrera E

    更新日期:1983-04-01 00:00:00

  • Beta-cell cytoplasmic Ca2+ balance as a determinant for glucose-stimulated insulin release.

    abstract::The introduction of new techniques and the access to clonal lines of insulin-secreting cells have enabled re-evaluation of glucose effects on Ca2+ movements in pancreatic beta cells. It became evident that glucose, in addition to stimulating the entry of Ca2+, also promotes active sequestration of the ion in intracell...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00281983

    authors: Hellman B

    更新日期:1985-08-01 00:00:00

  • Increased energy expenditure in poorly controlled Type 1 (insulin-dependent) diabetic patients.

    abstract::The basal energy expenditure of 10 Type 1 (insulin-dependent) C-peptide-negative diabetic patients (2042 +/- 62 kcal/24 h) was found to be significantly higher than the 1774 +/- 52 kcal/24 h predicted from their age, sex and body surface area (p less than 0.01). Intravenous insulin treatment significantly reduced ener...

    journal_title:Diabetologia

    pub_type: 杂志文章

    doi:10.1007/BF00253494

    authors: Nair KS,Halliday D,Garrow JS

    更新日期:1984-07-01 00:00:00