Abstract:
AIMS/HYPOTHESIS:Our recent studies suggest that activation of the wingless-type MMTV integration site (WNT) pathway plays pathogenic roles in diabetic retinopathy and age-related macular degeneration. Here we investigated the causative role of oxidative stress in retinal WNT pathway activation in an experimental model of diabetes. METHODS:Cultured retinal pigment epithelial cells and retinal capillary endothelial cells were treated with a lipid peroxidation product, 4-hydroxynonenal (HNE), and an antioxidant, N-acetyl-cysteine (NAC). In vivo, rats with streptozotocin-induced diabetes were treated by NAC for 8 weeks. Activation of the canonical WNT pathway was measured by TOPFLASH assay and by western blot analysis of WNT pathway components and a WNT target gene, Ctgf. Oxidative stress in the retina was evaluated by immunostaining of HNE and 3-nitrotyrosine. RESULTS:Levels of phosphorylated and total LDL receptor-related protein (LRP)6, and cytosolic β-catenin, as well as transcriptional activity of T cell factor (TCF)/β-catenin were significantly increased by HNE. The production of connective tissue growth factor (CTGF) was also upregulated by HNE. NAC blocked the WNT pathway activation induced by HNE. Furthermore, LRP6 stability was increased by HNE and decreased by NAC. Retinal levels of HNE and 3-nitrotyrosine were significantly increased in diabetic rats, compared with those in non-diabetic rats. In the same diabetic rat retinas, levels of LRP6, cytosolic β-catenin and CTGF were significantly increased. NAC treatment reduced HNE and 3-nitrotyrosine levels and attenuated the upregulation of LRP6, β-catenin and CTGF in diabetic rat retina. CONCLUSIONS/INTERPRETATION:Lipid peroxidation products activate the canonical WNT pathway through oxidative stress, which plays an important role in the development of retinal diseases.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Zhou T,Zhou KK,Lee K,Gao G,Lyons TJ,Kowluru R,Ma JXdoi
10.1007/s00125-010-1943-1subject
Has Abstractpub_date
2011-02-01 00:00:00pages
459-68issue
2eissn
0012-186Xissn
1432-0428journal_volume
54pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:One major objective of the St Vincent Declaration was to reduce the excess risk of myocardial infarction in patients with diabetes mellitus. We estimated the trend of the incidence and relative risk of myocardial infarction in the diabetic and non-diabetic populations in southern Germany from 1985 to 20...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-009-1434-4
更新日期:2009-09-01 00:00:00
abstract::The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400570
更新日期:1990-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 d...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-016-4190-2
更新日期:2017-03-01 00:00:00
abstract::The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR)...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00870139
更新日期:1986-12-01 00:00:00
abstract::Weaning onto chow diets causes the highest incidence of diabetes in the BB rat. Changes in gut development and absorption of nutrients in the diabetes prone rat and the subsequent effect on pancreatic function may play a role in the ultimate development of the disease. BB diabetes prone (dp) and BB normal (n) dams wer...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050762
更新日期:1997-08-01 00:00:00
abstract::Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00401372
更新日期:1992-12-01 00:00:00
abstract:AIM/HYPOTHESIS:The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To analyse these conseque...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-003-1149-x
更新日期:2003-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Effects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated. MATERIALS AND METHODS:INS-1 stable cell lines permitting inducible up- or downregulation of this transcription factor were...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0490-2
更新日期:2007-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed. METHODS:In this single-centre, double-blind, placebo-controlled, ...
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-017-4289-0
更新日期:2017-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Although insulin resistance has been associated with accumulations of specific intramuscular fatty acids and altered subcellular localisation of lipid droplets, these concepts remain controversial. Therefore, we aimed to identify specific intramuscular fatty acids and subcellular lipid localisations ass...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3169-0
更新日期:2014-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:Fractal analysis of the retinal vasculature provides a global measure of the complexity and density of retinal vessels summarised as a single variable: the fractal dimension. We investigated fractal dimensions as long-term predictors of microvasculopathy in type 1 diabetes. METHODS:We included 180 pati...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3317-6
更新日期:2014-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression is increased in diabeti...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3568-x
更新日期:2015-06-01 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::Diabetic retinopathy was found to be present in 12 out of a group of 67 diabetic patients supervised by us during 92 pregnancies, and 3 further pregnant diabetics were referred to us because of retinopathy. The mean duration of diabetes was 13 years (range 3--25 years). Nine patients had minimal retinopathy, 2 had bac...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00422254
更新日期:1978-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. METHODS:The study was performed within the Hoorn Study, a population-based study of glucose metabolism in indi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2864-6
更新日期:2013-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:Type 1 diabetes increases the risk of peripheral ischaemia and impairs recovery once ischaemia occurs, probably because the healing process is hampered by diabetes-induced endothelial dysfunction. In normoglycaemic mice subjected to limb ischaemia, blockade of nerve growth factor (NGF) compromises repar...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1424-5
更新日期:2004-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Insulin control of glucose output is a major mechanism by which appropriate amounts of glucose are produced to supply energy to the central nervous system, without causing long-term increases of the plasma glucose concentration. It is hypothesised that the primary route by which insulin maintains contro...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s001250051474
更新日期:2000-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Perinatal exposure to bisphenol A (BPA), a widely distributed environmental endocrine disruptor, is associated with insulin resistance and diabetes in offspring. The underlying molecular mechanisms could involve epigenetics, as adverse effects induced by environmental exposure in early life are suggeste...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2944-7
更新日期:2013-09-01 00:00:00
abstract::Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GDM) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes. It has been hypothesised that epigene...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-019-05011-8
更新日期:2019-12-01 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:Abnormal gut microbiota and blood metabolome profiles have been reported both in children and adults with uncomplicated type 1 diabetes as well as in adults with type 1 diabetes and advanced stages of diabetic nephropathy. In this study we aimed to investigate the gut microbiota and a panel of targeted ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05260-y
更新日期:2020-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:We examined whether diabetic background retinopathy is associated with reduced coronary vasoreactivity in people with Type 1 diabetes. METHODS:A total of 21 men with Type 1 diabetes were investigated, including 9 men with background retinopathy and 12 men without retinopathy. In addition, 12 non-diabet...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s00125-004-1340-8
更新日期:2004-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:The endogenous production of stromal cell-derived factor-1 (SDF-1) in beta cells in transgenic mice attenuates the development of diabetes in response to streptozotocin. Here we propose that beta cell injury induces SDF-1 production, and the SDF-1/chemokine (C-X-C motif) receptor 4 (CXCR4) interaction a...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2181-x
更新日期:2011-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Rosiglitazone, an insulin sensitiser, not only improves insulin sensitivity but also enhances insulin secretory capacity by ameliorating gluco- and lipotoxicity in beta cells. Rosiglitazone can stimulate insulin secretion at basal and high glucose levels via a phosphatidylinositol 3-kinase (PI3K)-depend...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-009-1337-4
更新日期:2009-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:We evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited. METHODS:The International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-019-05078-3
更新日期:2020-04-01 00:00:00
abstract::Studying 239 Type 1 (insulin-dependent) diabetic patients and 144 of their first-degree relatives, we found a significant prevalence of autoimmune manifestations in both groups, compared with sex- and age-matched control subjects (p less than 0.001). In particular, in diabetic patients we found a high frequency of aut...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00262215
更新日期:1984-06-01 00:00:00
abstract::The evolution of glucose assay methods has been central to the development of present therapies for diabetes mellitus. However, new blood glucose assay capabilities, such as convenient and truly continuous monitoring, are now needed to foster a new era of close blood glucose control. The principles and present status ...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s001250051418
更新日期:1997-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaem...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3636-2
更新日期:2015-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study wa...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4424-y
更新日期:2017-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:High intake of carbohydrates, particularly sucrose, in western societies is associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related primarily to the carbohydrate quantity or to the hormonal responses, particularly glucose-dependent...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3423-5
更新日期:2015-02-01 00:00:00