Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production.

Abstract:

:Many individuals with diabetes experience impaired cardiac contractility that cannot be explained by hypertension and atherosclerosis. This cardiomyopathy may be due to either organ-based damage, such as fibrosis, or to direct damage to cardiomyocytes. Reactive oxygen species (ROS) have been proposed to contribute to such damage. To address these hypotheses, we examined contractility, Ca(2+) handling, and ROS levels in individual cardiomyocytes isolated from control hearts, diabetic OVE26 hearts, and diabetic hearts overexpressing antioxidant protein metallothionein (MT). Our data showed that diabetic myocytes exhibited significantly reduced peak shortening, prolonged duration of shortening/relengthening, and decreased maximal velocities of shortening/relengthening as well as slowed intracellular Ca(2+) decay compared with control myocytes. Overexpressing MT prevented these defects induced by diabetes. In addition, high glucose and angiotensin II promoted significantly increased generation of ROS in diabetic cardiomyocytes. Chronic overexpression of MT or acute in vitro treatment with the flavoprotein inhibitor diphenyleneiodonium or the angiotensin II type I receptor antagonist losartan eliminated excess ROS production in diabetic cardiomyocytes. These data show that diabetes induces damage at the level of individual myocyte. Damage can be attributed to ROS production, and diabetes increases ROS production via angiotensin II and flavoprotein enzyme-dependent pathways.

journal_name

Diabetes

journal_title

Diabetes

authors

Ye G,Metreveli NS,Ren J,Epstein PN

doi

10.2337/diabetes.52.3.777

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

777-83

issue

3

eissn

0012-1797

issn

1939-327X

journal_volume

52

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Neonatal rat islet cell cultures synthesize insulin-like growth factor I.

    abstract::Monolayer cultures of islet B-cells were established from neonatal rat pancreas. Serum-free media conditioned by these cultures for 72 h were concentrated and fractionated on Sephadex G-50 at acid pH into a high-molecular-weight pool containing binding protein for insulin-like growth factors (IGFs) and a low-molecular...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.7.696

    authors: Romanus JA,Rabinovitch A,Rechler MM

    更新日期:1985-07-01 00:00:00

  • Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation.

    abstract::Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polyp...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:

    authors: van der Burg MP,Gooszen HG,Guicherit OR,Jansen JB,Frölich M,van Haastert FA,Lamers CB

    更新日期:1989-09-01 00:00:00

  • Conference on insulin pump therapy in diabetes. Multicenter study effect on microvascular disease. Studies of retinopathy. Methodology for assessment and classification with fundus photographs.

    abstract::A major goal of the study was to assess the methodologies available for the quantification of retinal lesions suitable for application in trials of metabolic management. We describe the methods used for grading stereoscopic color fundus photographs. Overall retinopathy severity level for each eye ranging from normal (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.3.s42

    authors: Davis MD,Hubbard LD,Trautman J,Klein R

    更新日期:1985-08-01 00:00:00

  • The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity-related comorbidities.

    abstract::Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individual...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0905

    authors: Villarreal-Molina MT,Aguilar-Salinas CA,Rodríguez-Cruz M,Riaño D,Villalobos-Comparan M,Coral-Vazquez R,Menjivar M,Yescas-Gomez P,Königsoerg-Fainstein M,Romero-Hidalgo S,Tusie-Luna MT,Canizales-Quinteros S,Metabolic Study Group.

    更新日期:2007-07-01 00:00:00

  • Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria.

    abstract::The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.6.745

    authors: Gambaro G,Baggio B,Cicerello E,Mastrosimone S,Marzaro G,Borsatti A,Crepaldi G

    更新日期:1988-06-01 00:00:00

  • Glucose potentiation of arginine-induced insulin secretion is impaired in subjects with a glucokinase Glu256Lys mutation.

    abstract::Insulin and glucagon release and insulin sensitivity were investigated in patients with glucokinase deficiency. Five subjects with a missense mutation (Glu256Lys) were studied. They were compared with six healthy subjects with low insulin response but normal glucose tolerance. Insulin and glucagon levels were measured...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.12.1402

    authors: Wajngot A,Alvarsson M,Glaser A,Efendic S,Luthman H,Grill V

    更新日期:1994-12-01 00:00:00

  • Detection of GAD65 antibodies in diabetes and other autoimmune diseases using a simple radioligand assay.

    abstract::Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). We have developed a simple, reproducible, and quantitative immunoprecipitation radioligand assay using as antigen in vitro transcribed and translated [35S]methionine-labeled human isle...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.3.459

    authors: Petersen JS,Hejnaes KR,Moody A,Karlsen AE,Marshall MO,Høier-Madsen M,Boel E,Michelsen BK,Dyrberg T

    更新日期:1994-03-01 00:00:00

  • Suppression of gluconeogenesis after a 3-day fast does not deplete liver glycogen in patients with NIDDM.

    abstract::To determine the effect of inhibition of gluconeogenesis on liver glycogen stores in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3-[...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.2.256

    authors: Clore JN,Blackard WG

    更新日期:1994-02-01 00:00:00

  • Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta1, and a Smad2-dependent mechanism.

    abstract::Thiazolidinediones, such as pioglitazone, seem to exert direct antiatherosclerotic and antirestenotic effects on type 2 diabetes, in part due to an induction of vascular smooth muscle cell (VSMC) apoptosis. We aimed to study the role of transforming growth factor (TGF)-beta in rat aortic VSMC. Pioglitazone at 100 micr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.3.811

    authors: Redondo S,Ruiz E,Santos-Gallego CG,Padilla E,Tejerina T

    更新日期:2005-03-01 00:00:00

  • Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women.

    abstract:OBJECTIVE:Recent genome-wide association studies (GWASs) related common variants in the interleukin-6 (Il-6) receptor (IL6R) gene to plasma C-reactive protein (CRP) concentrations. Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0968

    authors: Qi L,Rifai N,Hu FB

    更新日期:2009-01-01 00:00:00

  • Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    abstract::Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0291

    authors: Schafer MJ,White TA,Evans G,Tonne JM,Verzosa GC,Stout MB,Mazula DL,Palmer AK,Baker DJ,Jensen MD,Torbenson MS,Miller JD,Ikeda Y,Tchkonia T,van Deursen JM,Kirkland JL,LeBrasseur NK

    更新日期:2016-06-01 00:00:00

  • Dissociation of intestinal and hepatic activities of FXR and LXRα supports metabolic effects of terminal ileum interposition in rodents.

    abstract::The farnesoid X receptor (FXR) and the liver x receptors (LXRs) are bile acid-activated receptors that are highly expressed in the enterohepatic tissues. The mechanisms that support the beneficial effects of bariatric surgery are only partially defined. We have investigated the effects of ileal interposition (IT), a s...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0299

    authors: Mencarelli A,Renga B,D'Amore C,Santorelli C,Graziosi L,Bruno A,Monti MC,Distrutti E,Cipriani S,Donini A,Fiorucci S

    更新日期:2013-10-01 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

  • Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors.

    abstract::We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0808

    authors: Jarajapu YP,Bhatwadekar AD,Caballero S,Hazra S,Shenoy V,Medina R,Kent D,Stitt AW,Thut C,Finney EM,Raizada MK,Grant MB

    更新日期:2013-04-01 00:00:00

  • Disulfide Mispairing During Proinsulin Folding in the Endoplasmic Reticulum.

    abstract::Proinsulin folding within the endoplasmic reticulum (ER) remains incompletely understood, but it is clear that in mutant INS gene-induced diabetes of youth (MIDY), progression of the (three) native disulfide bonds of proinsulin becomes derailed, causing insulin deficiency, β-cell ER stress, and onset of diabetes. Here...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1345

    authors: Haataja L,Manickam N,Soliman A,Tsai B,Liu M,Arvan P

    更新日期:2016-04-01 00:00:00

  • Rapid detection of IDDM susceptibility with HLA-DQ beta-alleles as markers.

    abstract::The allelic forms of the human leukocyte antigen (HLA)-DQ beta-chain (DQB1) have been recognized as the best markers of insulin-dependent diabetes mellitus (IDDM) susceptibility. We describe a method that allows the recognition of these DQB1 alleles without the use of either allele-specific oligonucleotide probes or r...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.12.1617

    authors: Trucco G,Fritsch R,Giorda R,Trucco M

    更新日期:1989-12-01 00:00:00

  • Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.

    abstract::Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The object...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.3.508

    authors: Hansen L,Echwald SM,Hansen T,Urhammer SA,Clausen JO,Pedersen O

    更新日期:1997-03-01 00:00:00

  • Nutrient excess stimulates β-cell neogenesis in zebrafish.

    abstract::Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1841

    authors: Maddison LA,Chen W

    更新日期:2012-10-01 00:00:00

  • CD40 in Retinal Müller Cells Induces P2X7-Dependent Cytokine Expression in Macrophages/Microglia in Diabetic Mice and Development of Early Experimental Diabetic Retinopathy.

    abstract::Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and preve...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0051

    authors: Portillo JC,Lopez Corcino Y,Miao Y,Tang J,Sheibani N,Kern TS,Dubyak GR,Subauste CS

    更新日期:2017-02-01 00:00:00

  • Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus Study.

    abstract::It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro- and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleuki...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.4.1088

    authors: van Exel E,Gussekloo J,de Craen AJ,Frölich M,Bootsma-Van Der Wiel A,Westendorp RG,Leiden 85 Plus Study.

    更新日期:2002-04-01 00:00:00

  • Relationship between cerebrospinal fluid visfatin (PBEF/Nampt) levels and adiposity in humans.

    abstract:OBJECTIVE:Observations of elevated circulating concentrations of visfatin (PBEF/Nampt) in obesity and diabetes suggest that this recently described adipokine is involved in the regulation of body weight and metabolism. We examined in humans whether visfatin is found in cerebrospinal fluid (CSF) and, if so, how CSF visf...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-1176

    authors: Hallschmid M,Randeva H,Tan BK,Kern W,Lehnert H

    更新日期:2009-03-01 00:00:00

  • Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes.

    abstract::Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.12.2079

    authors: Parker JC,McPherson RK,Andrews KM,Levy CB,Dubins JS,Chin JE,Perry PV,Hulin B,Perry DA,Inagaki T,Dekker KA,Tachikawa K,Sugie Y,Treadway JL

    更新日期:2000-12-01 00:00:00

  • 3,4-Dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells.

    abstract::Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.8.2424

    authors: Justo P,Sanz AB,Egido J,Ortiz A

    更新日期:2005-08-01 00:00:00

  • Prevention of adoptive transfer in BB rats by prophylactic insulin treatment.

    abstract::Prophylactic insulin can prevent diabetes in the BB rat. We evaluated its use to prevent adoptive transfer of diabetes by activated splenocytes. ConA-activated spleen cells from acutely diabetic BB rats were divided into two equal aliquots and injected intravenously in paired diabetes-prone BB rat littermates. At the ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.10.1273

    authors: Bertrand S,De Paepe M,Vigeant C,Yale JF

    更新日期:1992-10-01 00:00:00

  • Growth Hormone Control of Hepatic Lipid Metabolism.

    abstract::In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relat...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0649

    authors: Liu Z,Cordoba-Chacon J,Kineman RD,Cronstein BN,Muzumdar R,Gong Z,Werner H,Yakar S

    更新日期:2016-12-01 00:00:00

  • Insulin resistance by uncleaved insulin proreceptor. Emergence of binding site by trypsin.

    abstract::Two sisters presented with severe insulin resistance and markedly decreased insulin binding to erythrocytes, cultured fibroblasts, and transformed lymphocytes. The dose-response curve of insulin-stimulated amino acid uptake in the fibroblasts was shifted to the right. The molecular weight of the insulin receptor on th...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.5.653

    authors: Kobayashi M,Sasaoka T,Takata Y,Hisatomi A,Shigeta Y

    更新日期:1988-05-01 00:00:00

  • Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism.

    abstract:OBJECTIVE:Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with ho...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0787

    authors: Suliman SG,Stanik J,McCulloch LJ,Wilson N,Edghill EL,Misovicova N,Gasperikova D,Sandrikova V,Elliott KS,Barak L,Ellard S,Volpi EV,Klimes I,Gloyn AL

    更新日期:2009-12-01 00:00:00

  • The nature of insulin secretory defect in aging rats.

    abstract::We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.11.1168

    authors: Draznin B,Steinberg JP,Leitner JW,Sussman KE

    更新日期:1985-11-01 00:00:00

  • Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis.

    abstract::The aim of this study was to investigate the effects of elevated D-glucose concentrations on vascular smooth muscle cell (VSMC) expression of the platelet-derived growth factor (PDGF)beta receptor and VSMC migratory behavior. Immunoprecipitation, immunofluorescent staining, and RT-PCR of human VSMCs showed that elevat...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.2.519

    authors: Campbell M,Allen WE,Silversides JA,Trimble ER

    更新日期:2003-02-01 00:00:00

  • Insulin-dependent childhood diabetes. Normal viability of cultured fibroblasts.

    abstract::Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inhere...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.27.3.338

    authors: Rosenbloom AL,Rosenbloom EK

    更新日期:1978-03-01 00:00:00