Abstract:
:Type 2 diabetes (T2D) is associated with vascular dysfunction. We hypothesized that increased nuclear factor-κB (NF-κB) signaling contributes to vascular dysfunction in T2D. We treated type 2 diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice with two NF-κB inhibitors (6 mg/kg dehydroxymethylepoxyquinomicin twice a week and 500 μg/kg/day IKK-NBD peptide) for 4 weeks. Pressure-induced myogenic tone was significantly potentiated, while endothelium-dependent relaxation (EDR) was impaired in small coronary arterioles and mesenteric resistance artery from diabetic mice compared with controls. Interestingly, diabetic mice treated with NF-κB inhibitors had significantly reduced myogenic tone potentiation and improved EDR. Importantly, vascular function was also rescued in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) double knockout mice compared with db(-)/db(-) mice. Additionally, the acute in vitro downregulation of NF-κB-p65 using p65NF-κB short hairpin RNA lentivirus in arteries from db(-)/db(-) mice also improved vascular function. The NF-κB inhibition did not affect blood glucose level or body weight. The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF-κB phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, and cyclooxygenase (COX)-2 expression were increased in arteries from diabetic mice, which were restored after NF-κB inhibition and in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) mice. In the current study, we provided evidence that enhanced NF-κB activity impairs vascular function by PARP-1-, Sp-1-, and COX-2-dependent mechanisms in male type 2 diabetic mice. Therefore, NF-κB could be a potential target to overcome diabetes-induced vascular dysfunction.
journal_name
Diabetesjournal_title
Diabetesauthors
Kassan M,Choi SK,Galán M,Bishop A,Umezawa K,Trebak M,Belmadani S,Matrougui Kdoi
10.2337/db12-1374subject
Has Abstractpub_date
2013-06-01 00:00:00pages
2078-87issue
6eissn
0012-1797issn
1939-327Xpii
db12-1374journal_volume
62pub_type
杂志文章相关文献
DIABETES文献大全abstract:OBJECTIVE:To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1704
更新日期:2010-06-01 00:00:00
abstract::The acquisition of T-cell tolerance in the thymus is limited to those antigens expressed in the thymus at the time of T-cell development. Normally, islet antigens that are involved in insulin-dependent diabetes mellitus (IDDM) are not present in the thymus, but we have previously shown that transplantation of islets e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.8.871
更新日期:1995-08-01 00:00:00
abstract::Tissue sensitivity to insulin was studied using the euglycemic insulin clamp technique (delta plasma insulin above basal 90 microU/ml) in eight patients with type I diabetes mellitus (IDDM) before and after 4-8 mo of continuous subcutaneous insulin infusion (CSII) and in 36 age-matched control subjects. Institution of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.3.s80
更新日期:1985-08-01 00:00:00
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
更新日期:1989-12-01 00:00:00
abstract:OBJECTIVE:Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, b...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1433
更新日期:2010-07-01 00:00:00
abstract::Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic beta-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca2+ concentration) ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.8.1942
更新日期:2004-08-01 00:00:00
abstract::A single administration of complete Freund's adjuvant (CFA), type 1 carrageenan (Car), or silica 7, 2, and 2 days, respectively, before infection with a low dose (1 x 10(2) plaque-forming units/mouse) of encephalomyocarditis D (EMC-D) virus resulted in a significant increase in the incidence of diabetes in SJL/J mice ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.12.1586
更新日期:1991-12-01 00:00:00
abstract::Adult, male ICR Swiss mice are susceptible to the diabetogenic effects of the D-variant of encephalomyocarditis virus (EMC-D) in contrast to adult C3H/HeJ male mice, which are relatively resistant. To date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. We hav...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.12.1217
更新日期:1985-12-01 00:00:00
abstract::Glucokinase is a critical component of the physiological glucose sensor found in cell types that are responsive to changes in plasma glucose levels. The acute regulation of glucokinase activity has been shown to occur via a regulatory protein found in liver parenchymal cells (Van Schaftingen E, Detheux M, Da Cunha MV....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.12.1670
更新日期:1996-12-01 00:00:00
abstract::The GK rat model of type 2 diabetes is especially convenient to dissect the pathogenic mechanism necessary for the emergence of overt diabetes because all adult rats obtained in our department (GK/Par colony) to date have stable basal mild hyperglycemia and because overt diabetes is preceded by a period of normoglycem...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2007.s89
更新日期:2001-02-01 00:00:00
abstract::Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treate...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1429
更新日期:2005-05-01 00:00:00
abstract::A significant increase in CO2 production, reflecting carbohydrate oxidation and/or fat synthesis, is observed in normal subjects after the ingestion of glucose. The anatomic site(s) of this CO2 production has not yet been localized, although liver and muscle are logical considerations. To assess the contribution of sk...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.10.960
更新日期:1985-10-01 00:00:00
abstract::The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. S...
journal_title:Diabetes
pub_type: 历史文章,杂志文章
doi:10.2337/diab.24.11.961
更新日期:1975-11-01 00:00:00
abstract::Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. We examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.11.2720
更新日期:2003-11-01 00:00:00
abstract::Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows: Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rap...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.1.1
更新日期:1975-01-01 00:00:00
abstract::Longitudinal electron-microscopic and morphometric studies of autonomic nerves containing predominantly parasympathetic fibers were undertaken in the spontaneously diabetic BB rat. Unmyelinated fibers of the diabetic vagus nerve and myelinated fibers of the penile nerve showed increased numbers of axonal glycogenosome...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.7.733
更新日期:1986-07-01 00:00:00
abstract::GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD) mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to be associated with the development of autoimmune diabetes. Hormonal changes through environmental stimuli are considered to influence the expression of the d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.9.2764
更新日期:2002-09-01 00:00:00
abstract::The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein respon...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.46.12.2082
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:Atherosclerotic cardiovascular disease is the leading cause of death among people with diabetes. Generation of oxidized LDLs and reduced nitric oxide (NO) availability because of endothelial NO synthase (eNOS) dysfunction are critical events in atherosclerotic plaque formation. Biochemical mechanism leading f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0167
更新日期:2009-10-01 00:00:00
abstract::In 112 obese compared with 42 lean children, we found that serum leptin is elevated early in the evolution of childhood-onset obesity (28.4 +/- 1.4 vs. 4.5 +/- 0.4 ng/ml in lean children, P < 0.0001) and correlates with adiposity. Obese children also had higher serum leptin normalized to fat mass. Despite high serum l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.6.989
更新日期:1997-06-01 00:00:00
abstract::Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.11.3347
更新日期:2002-11-01 00:00:00
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
更新日期:1999-10-01 00:00:00
abstract::Pancreatogenic diabetes (PD), secondary either to chronic calcific pancreatitis or to pancreatectomy, is characterized by higher frequency of hypoglycemic events during insulin therapy in comparison with type I insulin-dependent diabetes (IDD). Not only glucagon deficiency, but an enhanced peripheral tissue sensitivit...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.4.346
更新日期:1982-04-01 00:00:00
abstract::OKT3 has emerged as a highly effective antirejection therapy, but its efficacy in pancreas transplantation remains to be determined. During a 26-mo period, 46 vascularized pancreas transplants were performed with pancreaticoduodenocystostomy. Twenty-one patients (45.7%) were treated with OKT3. Indications for OKT3 use...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s74
更新日期:1989-01-01 00:00:00
abstract::Cyclic nucleotide phosphodiesterase (PDE) 3B plays an important role in the antilipolytic action of insulin and, thereby, the release of fatty acids from adipocytes. Increased concentrations of circulating fatty acids as a result of elevated or unrestrained lipolysis cause insulin resistance. The lipolytic action of t...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.631
更新日期:2002-03-01 00:00:00
abstract::Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. W...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.4.901
更新日期:2001-04-01 00:00:00
abstract::Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising ini...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1212
更新日期:2015-04-01 00:00:00
abstract::A simple method for the elimination of labile glycohemoglobin in the chromatographic quantitation of glycosylated hemoglobin is described. Use is made of the instability of Schiff base adducts in acidic solution. Erythrocytes are lysed with a pH 5 buffer. At this pH dissociation reaches completion during sample prepar...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.7.630
更新日期:1982-07-01 00:00:00
abstract::Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 20...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1557
更新日期:2003-06-01 00:00:00
abstract::Sirt6 is an NAD+-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. In this study, we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet-induced obesity, which was attributed to ad...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1225
更新日期:2017-05-01 00:00:00