Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process.

Abstract:

:Hyperglycemia-induced oxidative stress is detrimental for endothelial cells, contributing to the vascular complications of diabetes. The mitochondrial permeability transition pore (PTP) is an oxidative stress-sensitive channel involved in cell death; therefore, we have examined its potential role in endothelial cells exposed to oxidative stress or high glucose level. Metformin, an antihyperglycemic agent used in type 2 diabetes, was also investigated because it inhibits PTP opening in transformed cell lines. Cyclosporin A (CsA), the reference PTP inhibitor, and a therapeutic dose of metformin (100 micromol/l) led to PTP inhibition in permeabilized human microvascular endothelial cells (HMEC-1). Furthermore, exposure of intact HMEC-1 or primary endothelial cells from either human umbilical vein or bovine aorta to the oxidizing agent tert-butylhydroperoxide or to 30 mmol/l glucose triggered PTP opening, cytochrome c decompartmentalization, and cell death. CsA or metformin prevented all of these effects. The antioxidant N-acetyl-l-cysteine also prevented hyperglycemia-induced apoptosis. We conclude that 1) elevated glucose concentration leads to an oxidative stress that favors PTP opening and subsequent cell death in several endothelial cell types and 2) metformin prevents this PTP opening-related cell death. We propose that metformin improves diabetes-associated vascular disease both by lowering blood glucose and by its effect on PTP regulation.

journal_name

Diabetes

journal_title

Diabetes

authors

Detaille D,Guigas B,Chauvin C,Batandier C,Fontaine E,Wiernsperger N,Leverve X

doi

10.2337/diabetes.54.7.2179

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

2179-87

issue

7

eissn

0012-1797

issn

1939-327X

pii

54/7/2179

journal_volume

54

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Reduced glomerular sodium/potassium adenosine triphosphatase activity in acute streptozocin diabetes and its prevention by oral sorbinil.

    abstract::To explore metabolic changes associated with the sorbitol accumulation and myo-inositol depletion observed in glomeruli of rats with experimental diabetes, we examined total and ouabain-inhibited adenosine triphosphatase (ATPase) activity in glomeruli isolated from control and streptozocin (STZ)-diabetic rats. Glomeru...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.11.1071

    authors: Cohen MP,Dasmahapatra A,Shapiro E

    更新日期:1985-11-01 00:00:00

  • Exendin-4 suppresses SRC activation and reactive oxygen species production in diabetic Goto-Kakizaki rat islets in an Epac-dependent manner.

    abstract:OBJECTIVE:Reactive oxygen species (ROS) is one of most important factors in impaired metabolism secretion coupling in pancreatic β-cells. We recently reported that elevated ROS production and impaired ATP production at high glucose in diabetic Goto-Kakizaki (GK) rat islets are effectively ameliorated by Src inhibition,...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0021

    authors: Mukai E,Fujimoto S,Sato H,Oneyama C,Kominato R,Sato Y,Sasaki M,Nishi Y,Okada M,Inagaki N

    更新日期:2011-01-01 00:00:00

  • SOX4 Allows Facultative β-Cell Proliferation Through Repression of Cdkn1a.

    abstract::The high-mobility group box transcription factor SOX4 is the most highly expressed SOX family protein in pancreatic islets, and mutations in Sox4 are associated with an increased risk of developing type 2 diabetes. We used an inducible β-cell knockout mouse model to test the hypothesis that Sox4 is essential for the m...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1074

    authors: Xu EE,Sasaki S,Speckmann T,Nian C,Lynn FC

    更新日期:2017-08-01 00:00:00

  • Defective free-fatty acid and oxidative glucose metabolism in IDDM during hypoglycemia. Influence of glycemic control.

    abstract::To examine the impact of diabetes and its treatment on plasma free-fatty acid (FFA) and oxidative fuel metabolism during hypoglycemia, we combined indirect calorimetry with [3-3H]glucose during a 4-h low-dose insulin infusion (plasma insulin approximately 2-fold above basal) in six poorly controlled and nine well-cont...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章

    doi:10.2337/diab.39.2.134

    authors: Caprio S,Amiel S,Tamborlane WV,Gelfand RA,Sherwin RS

    更新日期:1990-02-01 00:00:00

  • Long-term study of mortality and vascular complications in juvenile-onset (type I) diabetes.

    abstract::A cohort of 372 insulin-dependent diabetic children, diagnosed between October 1949 and December 1960, were followed-up until December 1976 by the same team of physicians. At the time of diagnosis all patients were under 16 yr of age and were given standardized treatment which did not change from 1949 to 1976. The the...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.3.175

    authors: Lestradet H,Papoz L,Hellouin de Menibus C,Levavasseur F,Besse J,Billaud L,Battistelli F,Tric P,Lestradet F

    更新日期:1981-03-01 00:00:00

  • The angiotensin-converting enzyme DD genotype is associated with glomerulopathy lesions in type 2 diabetes.

    abstract::Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a fas...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.1.251

    authors: Solini A,Dalla Vestra M,Saller A,Nosadini R,Crepaldi G,Fioretto P

    更新日期:2002-01-01 00:00:00

  • Cholesterol metabolism in alloxan-induced diabetic rabbits.

    abstract::The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.39.5.626

    authors: O'Meara NM,Devery RA,Owens D,Collins PB,Johnson AH,Tomkin GH

    更新日期:1990-05-01 00:00:00

  • Reduced early insulin secretion in the etiology of type 2 diabetes mellitus in Pima Indians.

    abstract::We report the results of cross-sectional, prospective, and longitudinal studies identifying etiologic metabolic factors in the susceptibility to type 2 diabetes mellitus of the Pima Indians of Arizona, whose prevalence and incidence rates of the disease are the highest in the world. Diabetic Pima Indians are metabolic...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.51.2007.s262

    authors: Bogardus C,Tataranni PA

    更新日期:2002-02-01 00:00:00

  • Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.

    abstract::Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator-activated receptor (PPAR)-gamma response elements in v...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.5.1149

    authors: Ryder JW,Portocarrero CP,Song XM,Cui L,Yu M,Combatsiaris T,Galuska D,Bauman DE,Barbano DM,Charron MJ,Zierath JR,Houseknecht KL

    更新日期:2001-05-01 00:00:00

  • Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

    abstract::Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesized that the MGO scavenge...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0933

    authors: Li H,O'Meara M,Zhang X,Zhang K,Seyoum B,Yi Z,Kaufman RJ,Monks TJ,Wang JM

    更新日期:2019-06-01 00:00:00

  • Phenotypic correction of diabetic mice by adenovirus-mediated glucokinase expression.

    abstract::Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. GK levels are lowered in patients with maturity-onset diabetes of the young and in some diabetic animal models. Here, we explored t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.10.2287

    authors: Desai UJ,Slosberg ED,Boettcher BR,Caplan SL,Fanelli B,Stephan Z,Gunther VJ,Kaleko M,Connelly S

    更新日期:2001-10-01 00:00:00

  • Diet-induced muscle insulin resistance in rats is ameliorated by acute dietary lipid withdrawal or a single bout of exercise: parallel relationship between insulin stimulation of glucose uptake and suppression of long-chain fatty acyl-CoA.

    abstract::Chronic high-fat feeding in rats induces profound whole-body insulin resistance, mainly due to effects in oxidative skeletal muscle. The mechanisms of this reaction remain unclear, but local lipid availability has been implicated. The aim of this study was to examine the influence of three short-term physiological man...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.12.2022

    authors: Oakes ND,Bell KS,Furler SM,Camilleri S,Saha AK,Ruderman NB,Chisholm DJ,Kraegen EW

    更新日期:1997-12-01 00:00:00

  • A functional melanocortin system may be required for chronic CNS-mediated antidiabetic and cardiovascular actions of leptin.

    abstract:OBJECTIVE:We recently showed that leptin has powerful central nervous system (CNS)-mediated antidiabetic and cardiovascular actions. This study tested whether the CNS melanocortin system mediates these actions of leptin in diabetic rats. RESEARCH DESIGN AND METHODS:A cannula was placed in the lateral ventricle of Spra...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-1221

    authors: da Silva AA,do Carmo JM,Freeman JN,Tallam LS,Hall JE

    更新日期:2009-08-01 00:00:00

  • Effect of combined antisense oligonucleotides against high-glucose- and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability.

    abstract::The effect of combined antisense oligonucleotides (AS-oligos) against overexpression of extracellular matrix (ECM) components, fibronectin, laminin, and collagen IV and on cell monolayer permeability was examined in rat microvascular endothelial cells (RMECs) grown in high glucose medium and on retinal vascular permea...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:

    authors: Oshitari T,Polewski P,Chadda M,Li AF,Sato T,Roy S

    更新日期:2006-01-01 00:00:00

  • Dynamic imaging of endoplasmic reticulum Ca2+ concentration in insulin-secreting MIN6 Cells using recombinant targeted cameleons: roles of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2 and ryanodine receptors.

    abstract::The endoplasmic reticulum (ER) plays a pivotal role in the regulation of cytosolic Ca(2+) concentrations ([Ca(2+)](cyt)) and hence in insulin secretion from pancreatic beta-cells. However, the molecular mechanisms involved in both the uptake and release of Ca(2+) from the ER are only partially defined in these cells, ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.2007.s190

    authors: Varadi A,Rutter GA

    更新日期:2002-02-01 00:00:00

  • von Willebrand factor and development of diabetic nephropathy in IDDM.

    abstract::We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate les...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.8.971

    authors: Stehouwer CD,Stroes ES,Hackeng WH,Mulder PG,Den Ottolander GJ

    更新日期:1991-08-01 00:00:00

  • The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation.

    abstract::The antihyperglycemic drug dimethylbiguanide (DMB, also known as metformin) reduces the risk of cardiovascular complications in type 2 diabetes, although the mechanism(s) involved are unclear. DMB reduces glycosylation-related protein cross-linking, a process similar to fibrin cross-linking catalyzed by activated fact...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.1.189

    authors: Standeven KF,Ariëns RA,Whitaker P,Ashcroft AE,Weisel JW,Grant PJ

    更新日期:2002-01-01 00:00:00

  • Therapeutic impact of leptin on diabetes, diabetic complications, and longevity in insulin-deficient diabetic mice.

    abstract:OBJECTIVE:The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS:We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Ak...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-1795

    authors: Naito M,Fujikura J,Ebihara K,Miyanaga F,Yokoi H,Kusakabe T,Yamamoto Y,Son C,Mukoyama M,Hosoda K,Nakao K

    更新日期:2011-09-01 00:00:00

  • Abnormalities of cognitive functions in IDDM revealed by P300 event-related potential analysis. Comparison with short-latency evoked potentials and psychometric tests.

    abstract::The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.8.952

    authors: Pozzessere G,Valle E,de Crignis S,Cordischi VM,Fattapposta F,Rizzo PA,Pietravalle P,Cristina G,Morano S,di Mario U

    更新日期:1991-08-01 00:00:00

  • Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

    abstract::A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian B...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.837

    authors: Poulsen PL,Ebbehøj E,Arildsen H,Knudsen ST,Hansen KW,Mølgaard H,Mogensen CE

    更新日期:2001-04-01 00:00:00

  • A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice.

    abstract::In this article, we report on a nonobese C57BL/6 (B6) mouse model of NIDDM named Akita mouse, characterized by early age onset and autosomal dominant mode of inheritance. At 7 weeks of age, the mean morning blood glucose levels (mmol/l) under ad libitum feeding conditions were significantly higher (P < 0.01, analysis ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.5.887

    authors: Yoshioka M,Kayo T,Ikeda T,Koizumi A

    更新日期:1997-05-01 00:00:00

  • Antihyperglycemic effect of dehydroepiandrosterone analogue 16 alpha-fluoro-5-androsten-17-one in diabetic mice.

    abstract::The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.8.1105

    authors: Pashko LL,Schwartz AG

    更新日期:1993-08-01 00:00:00

  • New Understanding of β-Cell Heterogeneity and In Situ Islet Function.

    abstract::Insulin-secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific subpopulations with d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/dbi17-0040

    authors: Benninger RKP,Hodson DJ

    更新日期:2018-04-01 00:00:00

  • PPARδ activation protects endothelial function in diabetic mice.

    abstract::Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial funct...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0117

    authors: Tian XY,Wong WT,Wang N,Lu Y,Cheang WS,Liu J,Liu L,Liu Y,Lee SS,Chen ZY,Cooke JP,Yao X,Huang Y

    更新日期:2012-12-01 00:00:00

  • Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes.

    abstract:OBJECTIVE:We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes-associated variants in the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), ADAMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0436

    authors: Grarup N,Andersen G,Krarup NT,Albrechtsen A,Schmitz O,Jørgensen T,Borch-Johnsen K,Hansen T,Pedersen O

    更新日期:2008-09-01 00:00:00

  • Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes.

    abstract::One subtype of maturity-onset diabetes of the young (MODY)-3 results from mutations in the gene encoding hepatocyte nuclear factor (HNF)-1 alpha. We generated transgenic mice expressing a naturally occurring dominant-negative form of human HNF-1 alpha (P291fsinsC) in pancreatic beta-cells. A progressive hyperglycemia ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.1.114

    authors: Yamagata K,Nammo T,Moriwaki M,Ihara A,Iizuka K,Yang Q,Satoh T,Li M,Uenaka R,Okita K,Iwahashi H,Zhu Q,Cao Y,Imagawa A,Tochino Y,Hanafusa T,Miyagawa J,Matsuzawa Y

    更新日期:2002-01-01 00:00:00

  • Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study.

    abstract::We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.2.202

    authors: Singer DE,Nathan DM,Anderson KM,Wilson PW,Evans JC

    更新日期:1992-02-01 00:00:00

  • Hepatic notch signaling correlates with insulin resistance and nonalcoholic fatty liver disease.

    abstract::Hepatic Notch signaling is inappropriately activated in obese/insulin-resistant mouse models. Genetic or pharmacologic inhibition of hepatic Notch signaling in obese mice simultaneously improves glucose tolerance and reduces hepatic triglyceride content. As such, we predicted that Notch signaling in human liver would ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0769

    authors: Valenti L,Mendoza RM,Rametta R,Maggioni M,Kitajewski C,Shawber CJ,Pajvani UB

    更新日期:2013-12-01 00:00:00

  • Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

    abstract::Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.10.1156

    authors: Haffner SM,Stern MP,Miettinen H,Gingerich R,Bowsher RR

    更新日期:1995-10-01 00:00:00

  • Cytosolic insulin-degrading activity in islet-derived tumor cell lines and in normal rat islets.

    abstract::RIN-m cells, cultured from a rat insulinoma, not only bind and secrete but also degrade insulin (Diabetes 1982; 31:521-31). The insulin-degrading activity resides in the cytosol and is similar to the insulin-specific proteases previously described in muscle and other tissues. It has an apparent Km of 0.15 microM for p...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.2.121

    authors: Bhathena SJ,Timmers KI,Oie HK,Voyles NR,Recant L

    更新日期:1985-02-01 00:00:00