Sequence variation in PPARG may underlie differential response to troglitazone.

Abstract:

:Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPARG) agonists used to treat type 2 diabetes. TZDs can also be used to reduce rates of type 2 diabetes in at-risk individuals. However, a large fraction of TZD-treated patients (30-40%) do not respond to TZD treatment with an improvement in insulin sensitivity (Si). We hypothesized that variation within the gene encoding PPARG may underlie this differential response to TZD therapy. We screened approximately 40 kb of PPARG in 93 nondiabetic Hispanic women (63 responders and 30 nonresponders) with previous gestational diabetes who had participated in the Troglitazone In the Prevention Of Diabetes study. TZD nonresponse was defined as the lower tertile in change in Si after 3 months of treatment. Baseline demographic and clinical measures were not different between responders and nonresponders. We identified and genotyped 131 variants including 126 single nucleotide polymorphisms and 5 insertion-deletion polymorphisms. Linkage disequilibrium analysis identified five haplotype blocks. Eight variants were associated with TZD response (P < 0.05). Three variants were also associated with changes in Si as a continuous variable. Our results suggest that PPARG variation may underlie response to TZD therapy in women at risk for type 2 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Wolford JK,Yeatts KA,Dhanjal SK,Black MH,Xiang AH,Buchanan TA,Watanabe RM

doi

10.2337/diabetes.54.11.3319

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

3319-25

issue

11

eissn

0012-1797

issn

1939-327X

pii

54/11/3319

journal_volume

54

pub_type

杂志文章,随机对照试验

相关文献

DIABETES文献大全
  • Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control.

    abstract::Studies have shown associations between exposure to hypoglycemia and increased mortality, raising the possibility that hypoglycemia has adverse cardiovascular effects. In this study, we determined the acute effects of hypoglycemia on cardiovascular autonomic control. Seventeen healthy volunteers were exposed to experi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0871

    authors: Rao AD,Bonyhay I,Dankwa J,Baimas-George M,Kneen L,Ballatori S,Freeman R,Adler GK

    更新日期:2016-01-01 00:00:00

  • Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.

    abstract::Diabetic nephropathy is characterized by hypertension and a relentless decline in kidney function. Angiotensin-converting enzyme inhibitors have been claimed to preserve kidney function better than an equal blood pressure (BP) reduction with conventional antihypertensive treatment (renoprotection). We compared the eff...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.43.9.1108

    authors: Nielsen FS,Rossing P,Gall MA,Skøtt P,Smidt UM,Parving HH

    更新日期:1994-09-01 00:00:00

  • The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human w

    abstract:OBJECTIVE:The purpose of this work was to determine the pattern of genes regulated by peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (PGC-1 alpha) in human adipocytes and the involvement of PPARalpha and PPARgamma in PGC-1 alpha transcriptional action. RESEARCH DESIGN AND METHODS:Primary c...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1465

    authors: Mazzucotelli A,Viguerie N,Tiraby C,Annicotte JS,Mairal A,Klimcakova E,Lepin E,Delmar P,Dejean S,Tavernier G,Lefort C,Hidalgo J,Pineau T,Fajas L,Clément K,Langin D

    更新日期:2007-10-01 00:00:00

  • Triggering and amplifying pathways of regulation of insulin secretion by glucose.

    abstract::Glucose stimulates insulin secretion by generating triggering and amplifying signals in beta-cells. The triggering pathway is well characterized. It involves the following sequence of events: entry of glucose by facilitated diffusion, metabolism of glucose by oxidative glycolysis, rise in the ATP-to-ADP ratio, closure...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.49.11.1751

    authors: Henquin JC

    更新日期:2000-11-01 00:00:00

  • Effects of exogenous fatty acid concentration on glucagon-induced changes in hepatic fatty acid metabolism.

    abstract::Studies were conducted to clarify the relationship between the external fatty acid concentration and glucagon in the regulation of hepatic fatty acid metabolism. Hepatocytes from fed rats were incubated with increasing concentrations of oleate (up to 1 mM) in the presence and absence of glucagon and the time sequence ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.3.236

    authors: McGarry JD,Foster DW

    更新日期:1980-03-01 00:00:00

  • Oxidative Stress Inhibits Healthy Adipose Expansion Through Suppression of SREBF1-Mediated Lipogenic Pathway.

    abstract::Recent studies have emphasized the association of adipose oxidative stress (Fat reactive oxygen species [ROS]) with the pathogenesis of metabolic disorders in obesity. However, the causal roles of Fat ROS in metabolic disturbances in vivo remain unclear because no mouse model has been available in which oxidative stre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1032

    authors: Okuno Y,Fukuhara A,Hashimoto E,Kobayashi H,Kobayashi S,Otsuki M,Shimomura I

    更新日期:2018-06-01 00:00:00

  • Undersulfation of glomerular basement membrane heparan sulfate in experimental diabetes and lack of correction with aldose reductase inhibition.

    abstract::In this study we examined the effect of experimental diabetes and of treatment with an aldose reductase inhibitor on the level of sulfation of glomerular basement membrane (GBM) heparan sulfate, the principal glycosaminoglycan in this extracellular matrix. Glycosaminoglycans were isolated from GBM purified from contro...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.10.1324

    authors: Cohen MP,Klepser H,Wu VY

    更新日期:1988-10-01 00:00:00

  • Emerging Role of Bone Morphogenetic Protein 4 in Metabolic Disorders.

    abstract::Bone morphogenetic proteins (BMPs) are a group of signaling molecules that belong to the TGF-β superfamily. Initially discovered for their ability to induce bone formation, BMPs are known to play a diverse and critical array of biological roles. We here focus on recent evidence showing that BMP4 is an important regula...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db20-0884

    authors: Baboota RK,Blüher M,Smith U

    更新日期:2021-02-01 00:00:00

  • Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation.

    abstract:OBJECTIVE:Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. RESEARCH DESIGN AND METHODS:Forearm skeletal musc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0857

    authors: Jocken JW,Roepstorff C,Goossens GH,van der Baan P,van Baak M,Saris WH,Kiens B,Blaak EE

    更新日期:2008-07-01 00:00:00

  • Insulin-pump treatment of pancreas-graft rejection.

    abstract::Continuous subcutaneous insulin infusion (CSII) was combined with antirejection therapy in four diabetic recipients of pancreas and kidney grafts with persisting hyperglycemia due to pancreas rejection. In three of the patients, full function of the pancreas was restored after as many as 40, 86, and 139 days of CSII. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.1.s71

    authors: Bartos V,Vanĕk I,Dryáková M,Saudek F,Malý J

    更新日期:1989-01-01 00:00:00

  • Use of dexamethasone in treatment of insulin lipoatrophy.

    abstract::To treat insulin lipoatrophy, small amounts of dexamethasone (4 micrograms/unit) were added to insulin injections in nine patients. Six cases showed significant improvement of dexamethasone-treated sites over that of control sites in six months. With the continued use of dexamethasone-containing insulin, they remained...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.26.4.296

    authors: Kumar O,Miller L,Mehtalia S

    更新日期:1977-04-01 00:00:00

  • Cx36 preferentially connects beta-cells within pancreatic islets.

    abstract::Previous studies have provided evidence for the transcripts of Cx43 and Cx45 within pancreatic islets. As of yet, however, it has proven difficult to unambiguously demonstrate the expression of these proteins by islet cells. We have investigated whether Cx36, a new connexin species recently identified in mammalian bra...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.5.727

    authors: Serre-Beinier V,Le Gurun S,Belluardo N,Trovato-Salinaro A,Charollais A,Haefliger JA,Condorelli DF,Meda P

    更新日期:2000-05-01 00:00:00

  • Effect of omega-3 fatty acids in diet of type I diabetic subjects on lipid values and hemorheological parameters.

    abstract::Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (omega 6FA...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.11.1412

    authors: Rillaerts EG,Engelmann GJ,Van Camp KM,De Leeuw I

    更新日期:1989-11-01 00:00:00

  • Effect of coxsackievirus B4 infection in mice on expression of 64,000-Mr autoantigen and glucose sensitivity of islets before development of hyperglycemia.

    abstract::Diabetogenic strains of Coxsackievirus B4 (CB4) produce a diabetes syndrome in susceptible mice that resembles insulin-dependent diabetes mellitus. To assess the possible role of autoimmunity, the expression of a 64,000-Mr islet antigen in SJL/J and CD1 mice infected with a diabetogenic strain of CB4 was monitored in ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.10.1419

    authors: Gerling I,Nejman C,Chatterjee NK

    更新日期:1988-10-01 00:00:00

  • Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump.

    abstract::Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.5.398

    authors: Bergenstal RM,Polonsky KS,Pons G,Jaspan JB,Rubenstein AH

    更新日期:1983-05-01 00:00:00

  • Dense core vesicle proteins IA-2 and IA-2beta: metabolic alterations in double knockout mice.

    abstract::IA-2 and IA-2beta are members of the transmembrane protein tyrosine phosphatase family located in dense core vesicles of neuroendocrine cells, including the beta-cells of pancreatic islets. In the present study, by mating C57BL/6Nci IA-2(+/-) with IA-2beta(+/-) mice, we generated double knockout mice (IA-2(-/-)/IA-2be...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.suppl_2.s46

    authors: Kubosaki A,Nakamura S,Notkins AL

    更新日期:2005-12-01 00:00:00

  • Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

    abstract::Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sam...

    journal_title:Diabetes

    pub_type: 杂志文章,多中心研究

    doi:10.2337/diab.45.11.1547

    authors: Karter AJ,Mayer-Davis EJ,Selby JV,D'Agostino RB Jr,Haffner SM,Sholinsky P,Bergman R,Saad MF,Hamman RF

    更新日期:1996-11-01 00:00:00

  • Calcium-calmodulin-dependent myosin phosphorylation by pancreatic islets.

    abstract::Pancreatic islets contain enzyme activity which catalyzes the phosphorylation by MgATP of cardiac, skeletal, or smooth muscle myosin light chains. The enzyme is activated by calcium (Ka = 10 microM) and calmodulin (Ka = 2 nM) and inhibited by trifluoperazine (Ki = 10 microM), a known inhibitor of calmodulin and of ins...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.31.6.566

    authors: MacDonald MJ,Kowluru A

    更新日期:1982-06-01 00:00:00

  • Endogenous Fatty Acids Are Essential Signaling Factors of Pancreatic β-Cells and Insulin Secretion.

    abstract::The secretion of insulin from β-cells depends on extracellular factors, in particular glucose and other small molecules, some of which act on G-protein-coupled receptors. Fatty acids (FAs) have been discussed as exogenous secretagogues of insulin for decades, especially after the FA receptor GPR40 (G-protein-coupled r...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1215

    authors: Hauke S,Keutler K,Phapale P,Yushchenko DA,Schultz C

    更新日期:2018-10-01 00:00:00

  • Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice.

    abstract::Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) allevia...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0662

    authors: Nagata N,Xu L,Kohno S,Ushida Y,Aoki Y,Umeda R,Fuke N,Zhuge F,Ni Y,Nagashimada M,Takahashi C,Suganuma H,Kaneko S,Ota T

    更新日期:2017-05-01 00:00:00

  • Classification, differential diagnosis, and staging of diabetic peripheral neuropathy.

    abstract::The peripheral nerve disorders associated with diabetes are complex and probably involve a variety of causative mechanisms. This may give rise to difficulty in the classification of individual cases. A broad separation into rapidly reversible or more persistent phenomena is helpful. The former, which can be categorize...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.46.2.s54

    authors: Thomas PK

    更新日期:1997-09-01 00:00:00

  • Leptin resistance during aging is independent of fat mass.

    abstract::Increased fat mass, abdominal adiposity, and insulin resistance are typical findings in aging mammals and are frequently associated with leptin resistance and increased plasma leptin levels. To examine whether leptin's failure in aging is due to aging per se or to changes in body fat mass or distribution, we studied a...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.4.1016

    authors: Gabriely I,Ma XH,Yang XM,Rossetti L,Barzilai N

    更新日期:2002-04-01 00:00:00

  • Handicaps to host defense. Effects of hyperglycemia on C3 and Candida albicans.

    abstract::The hyperglycemic patient remains persistently at risk for infectious complications. Whether ascribable to diabetes mellitus, to the administration of glucocorticoids, or to the infusion of hyperalimentation fluids, hyperglycemia may impair several mechanisms of humoral host defense, including such varied neutrophil f...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.39.3.271

    authors: Hostetter MK

    更新日期:1990-03-01 00:00:00

  • Elevated islet amyloid pancreatic polypeptide and proinsulin in lean gestational diabetes.

    abstract::Recent research indicates that islet amyloid pancreatic polypeptide (IAPP) might have a regulatory effect on beta-cell insulin processing and secretion. To study such interaction in more detail, IAPP secretion and kinetics and the serum concentrations of proinsulin were assessed both before and after delivery in lean ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.4.607

    authors: Kautzky-Willer A,Thomaseth K,Ludvik B,Nowotny P,Rabensteiner D,Waldhäusl W,Pacini G,Prager R

    更新日期:1997-04-01 00:00:00

  • AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5.

    abstract:OBJECTIVE:Insulin resistance associated with obesity and diabetes is ameliorated by specific overexpression of GLUT4 in skeletal muscle. The molecular mechanisms regulating skeletal muscle GLUT4 expression remain to be elucidated. The purpose of this study was to examine these mechanisms. RESEARCH DESIGN AND METHODS A...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0843

    authors: McGee SL,van Denderen BJ,Howlett KF,Mollica J,Schertzer JD,Kemp BE,Hargreaves M

    更新日期:2008-04-01 00:00:00

  • Disruption of hepatocyte growth factor/c-Met signaling enhances pancreatic beta-cell death and accelerates the onset of diabetes.

    abstract:OBJECTIVE:To determine the role of hepatocyte growth factor (HGF)/c-Met on β-cell survival in diabetogenic conditions in vivo and in response to cytokines in vitro. RESEARCH DESIGN AND METHODS:We generated pancreas-specific c-Met-null (PancMet KO) mice and characterized their response to diabetes induced by multiple l...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1305

    authors: Mellado-Gil J,Rosa TC,Demirci C,Gonzalez-Pertusa JA,Velazquez-Garcia S,Ernst S,Valle S,Vasavada RC,Stewart AF,Alonso LC,Garcia-Ocaña A

    更新日期:2011-02-01 00:00:00

  • Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    abstract::Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships betwee...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0407

    authors: Pepino MY,Eisenstein SA,Bischoff AN,Klein S,Moerlein SM,Perlmutter JS,Black KJ,Hershey T

    更新日期:2016-09-01 00:00:00

  • A reduced-fat diet and aerobic exercise in Japanese Americans with impaired glucose tolerance decreases intra-abdominal fat and improves insulin sensitivity but not beta-cell function.

    abstract::Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin s...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diabetes.54.2.340

    authors: Carr DB,Utzschneider KM,Boyko EJ,Asberry PJ,Hull RL,Kodama K,Callahan HS,Matthys CC,Leonetti DL,Schwartz RS,Kahn SE,Fujimoto WY

    更新日期:2005-02-01 00:00:00

  • Hepatocyte nuclear factor-4gamma: cDNA sequence, gene organization, and mutation screening in early-onset autosomal-dominant type 2 diabetes.

    abstract::The aim of this study was to investigate whether mutations in hepatocyte nuclear factor (HNF)-4gamma, a transcription factor homologous to HNF-4alpha, contribute to the etiology of early-onset type 2 diabetes. Linkage between diabetes and two polymorphic markers at the HNF-4gamma locus (D8S286 and D8S548) was evaluate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.10.2099

    authors: Plengvidhya N,Antonellis A,Wogan LT,Poleev A,Borgschulze M,Warram JH,Ryffel GU,Krolewski AS,Doria A

    更新日期:1999-10-01 00:00:00

  • Production of endothelin 1 by cultured bovine retinal endothelial cells and presence of endothelin receptors on associated pericytes.

    abstract::Endothelinlike immunoreactivity was detected by radioimmunoassay in medium conditioned by cultured endothelial cells obtained from bovine retinal microvessels (9.2 +/- 6.5 pM, n = 4). Sephadex G-25 column chromatography and fast-protein liquid chromatography revealed that most of the endothelinlike immunoreactivity wa...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.9.1200

    authors: Takahashi K,Brooks RA,Kanse SM,Ghatei MA,Kohner EM,Bloom SR

    更新日期:1989-09-01 00:00:00