Abstract:
AIMS/HYPOTHESIS:Increased expression and decreased degradation of extracellular matrix (ECM) proteins are key features of chronic diabetic complications. Fibronectin, a predominant ECM protein, has been shown to be overexpressed in all target organs of diabetic complications and in endothelial cells cultured in high levels of glucose. The present study was designed to elucidate the role of protein kinase B (Akt/PKB) in glucose-induced fibronectin mRNA expression and protein production in vascular endothelial cells. METHODS:Human umbilical vein endothelial cells were cultured in the presence of high glucose to study Akt/PKB activation. The upstream and downstream mediators in the Akt/PKB pathway were also investigated using dominant negative transfections and specific inhibitors of signalling pathways. Cells were subjected to real time RT-PCR, western blotting, and confocal microscopy to assess Akt1/PKBalpha activation and fibronectin mRNA expression and protein production. To detect transcription factor activation, electrophoretic mobility shift assay was carried out. RESULTS:Our data demonstrate that fibronectin mRNA expression and protein production that are induced by high glucose are mediated via activation of Akt/PKB, which is modulated by mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C. Glucose-induced fibronectin mRNA expression and protein production are also mediated by Akt1/PKBalpha-dependent activation of the transcription factors nuclear factor-kappaB and activating protein-1. CONCLUSIONS/INTERPRETATION:Our study provides insight into the mechanical basis of glucose-induced increases in fibronectin mRNA expression and protein production. High levels of glucose may increase fibronectin mRNA expression and protein production by activating Akt/PKB.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Xin X,Khan ZA,Chen S,Chakrabarti Sdoi
10.1007/s00125-005-1939-4subject
Has Abstractpub_date
2005-11-01 00:00:00pages
2428-36issue
11eissn
0012-186Xissn
1432-0428journal_volume
48pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptory (PPARgamma). We hypothesized that the anti-diabetic mechanism of thia...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051218
更新日期:1999-06-01 00:00:00
abstract::It has been suggested that bradykinin stimulates glucose uptake in experiments in vivo and in cultured cells. However, its mechanism has not yet been fully elucidated. In this study, the effects of bradykinin on the insulin signalling pathway were evaluated in isolated dog adipocytes. The bradykinin receptor binding s...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400672
更新日期:1996-04-01 00:00:00
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
更新日期:2016-09-01 00:00:00
abstract::Diabetes affects 4 to 5% of the population worldwide and is the most common metabolic disorder. The number of individuals diagnosed with diabetes is rapidly increasing, especially in the developed countries and the disorder frequently leads to secondary complications such as retinopathy, nephropathy, neuropathy and ca...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s001250100623
更新日期:2001-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:We aimed to determine the association of depression with dementia risk in people with type 2 diabetes, and to explore the possible mediating role of inflammation in this relationship. METHODS:The Edinburgh Type 2 Diabetes Study is a prospective cohort of 1066 men and women with type 2 diabetes aged 60-...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05301-6
更新日期:2021-02-01 00:00:00
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
更新日期:1995-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:The glomerular endothelial layer is coated by the endothelial surface layer (ESL), which is suggested to play a role in regulation of the permselectivity of macromolecules. Production of heparanase, a degrading enzyme of the ESL, is induced by reactive oxygen species (ROS). We hypothesised that oxidativ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-010-1810-0
更新日期:2010-09-01 00:00:00
abstract::Non-obese diabetic mice aged 30 to 60 days were treated orally with Cyclosporin at doses of 25, 15 and 2.5 mg/kg every 2 days until 160 days of age. Diabetes developed in 12 out of 18 oil-treated mice (67%), with partial to complete Langerhans' islet destruction associated with lymphocytic infiltration. The non-obese ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00454884
更新日期:1986-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:Insulin resistance is linked with a cluster of multiple risk factors and excessive acceleration of atherosclerosis. The underlying mechanism is not, however, fully understood. METHODS:To determine the link between insulin resistance and altered vascular function, we focused on the effect of various non...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051668
更新日期:2001-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:It is difficult to use HbA(1c) as an indicator of glycaemic control in patients with neonatal diabetes mellitus (NDM) because of high levels of fetal haemoglobin (HbF) remaining in the blood. In this study, glycated albumin (GA), which is not affected by HbF, and HbA(1c) were compared to evaluate whethe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2211-8
更新日期:2011-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:Knowledge of the within-subject variability of a parameter is required to properly design and calculate sample sizes for longitudinal studies. We sought to determine the day-to-day variability of measures of beta cell function derived from an OGTT. METHODS:Thirty-seven adults (13 with normal glucose to...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s00125-007-0819-5
更新日期:2007-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Epithelium-mesenchyme interactions play a major role in pancreas development. Recently, we demonstrated that embryonic pancreatic mesenchyme enhanced progenitor cell proliferation but inhibited endocrine cell differentiation. Here, we investigated the role played by sulphated proteoglycans, which are kn...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0571-2
更新日期:2007-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes. METHODS:We used fasting blood samples and longitudinal weight data for 5,436 adults (5,734 observatio...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3284-y
更新日期:2014-09-01 00:00:00
abstract::The concentrations of zinc, copper, and chromium in liver, kidney, muscle, bone and serum from control normoinsulinaemic and hyperinsulinaemic sand rats (Psammomys obesus) and from untreated spontaneously hyperinsulinaemic-hyperglycaemic sand rats were compared. A chronic hyperinsulinaemic-hyperglycaemic state was ass...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00277416
更新日期:1988-05-01 00:00:00
abstract::We performed i.v. insulin tolerance test in 30 non-obese (BMI < 30 male and < 28 female) non-diabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (K(itt) values). Then we compared the tyrosine-kinase activity of immunopurif...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF02369353
更新日期:1995-01-01 00:00:00
abstract::Analysis of the plasma from a totally pancreatectomized patient, with antiserum 30 K, has demonstrated basal glucagon immunoreactivity (GIR) levels in the normal range (80-110 pg/ml). Neither i. v. arginine nor oral glucose affected these GIR values, thus indicating the absence of functioning pancreatic or gastrointes...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01220639
更新日期:1976-12-01 00:00:00
abstract:AIM/HYPOTHESIS:Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not w...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-002-1026-z
更新日期:2003-02-01 00:00:00
abstract::From December, 1966 through 1990, 3082 pancreas transplants were reported to the International Registry. A detailed analysis was performed on the 2087 transplants in the 1986-90 data base; during this time the overall one year recipient and graft functional survival rates were 89% and 62%. Univariate analyses showed g...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00587615
更新日期:1991-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to investigate the effects of a secondary renal insult, due to chronic infusion of AGEs on renal function, and on early pathological markers in rats with a developmental nephron deficit. METHODS:Female Wistar-Kyoto rats were fed a low-protein diet (LPD; 8.7% casein) or a norma...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0175-x
更新日期:2006-04-01 00:00:00
abstract::Insulin release and 86Rb efflux were studied in perifused rat islets exposed in vitro to alloxan (2 mmol/l) for 5 min. At a low glucose concentration, alloxan transiently increased 86Rb efflux. Alloxan immediately and completely abolished the secretory response to glucose (15 mmol/l) and markedly delayed the reduction...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01221952
更新日期:1979-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). MET...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2913-1
更新日期:2013-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2'-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the path...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051258
更新日期:1999-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-003-1154-0
更新日期:2003-08-01 00:00:00
abstract::We have previously reported that oxygen free radical scavengers protect rat islet cells from damage by cytokines and we interpreted these findings as suggesting the involvement of oxygen free radicals but did not directly measure indices of free radical activity. In this study, we report on malondialdehyde, an end pro...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF02342435
更新日期:1992-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:We aimed to identify microRNAs (miRNAs) associated with type 2 diabetes and risk of developing the disease in skeletal muscle biopsies from phenotypically well-characterised twins. METHODS:We measured muscle miRNA levels in monozygotic (MZ) twins discordant for type 2 diabetes using arrays. Further inv...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3434-2
更新日期:2015-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Chemokines are chemotactic cytokines controlling the recruitment of leukocytes from the blood by regulating integrin adhesiveness. It has been shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant chemokin...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-002-0879-5
更新日期:2002-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:A shift towards younger age at onset of diabetes in susceptible people has been suggested as a possible explanation for the increasing temporal trend in incidence of type 1 diabetes. We aimed to test this hypothesis by assessing trends in incidence rates in the period 1984-2004 in children and young adu...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-009-1538-x
更新日期:2009-12-01 00:00:00
abstract::A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00399954
更新日期:1993-03-01 00:00:00
abstract::Previous study have reported a significant improvement of peripheral neuropathy following combined pancreas and kidney transplantation attributed to improvement of blood glucose control by some authors and to elimination of uraemia by others. To asses the specific role of uraemia and hyperglycaemia in neuropathy, 16 d...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00587632
更新日期:1991-08-01 00:00:00
abstract::The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TERalb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enroll...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s001250051114
更新日期:1999-01-01 00:00:00