Abstract:
AIM/HYPOTHESIS:Oxidative stress was shown to selectively induce impaired metabolic response to insulin, raising the possible involvement of alterations in Insulin-Receptor-Substrate (IRS) proteins. This study was conducted to assess whether oxidative stress induced IRS protein degradation and enhanced serine phosphorylation, and to assess their functional importance. METHODS:3T3-L1 adipocytes and rat hepatoma cells (FAO) were exposed to micro-molar H(2)O(2) by adding glucose oxidase to the culture medium, and IRS1 content, its serine phosphorylation and downstream metabolic insulin effects were measured. RESULTS:Cells exposed to oxidative stress exhibited decreased IRS1 (but not IRS2) content, and increased serine phosphorylation of both proteins. Total protein ubiquitination was increased in oxidized cells, but not in cells exposed to prolonged insulin treatment. Yet, lactacystin and MG132, two unrelated proteasome inhibitors, prevented IRS1 degradation induced by prolonged insulin but not by oxidative stress. The PI 3-kinase inhibitor LY294002 and the mTOR inhibitor rapamycin, but not the MEK1 inhibitor PD98059, could prevent IRS1 changes in oxidized cells. Rapamycin, which protected against IRS1 degradation and serine phosphorylation was not associated with improved response to acute insulin stimulation. Moreover, the antioxidant alpha lipoic acid, while protecting against oxidative stress-induced insulin resistance in 3T3-L1 adipocytes, could not prevent IRS1 degradation and serine phosphorylation. CONCLUSION/INTERPRETATION:Oxidative stress induces serine phosphorylation of IRS1 and increases its degradation by a proteasome-independent pathway; yet, these changes do not correlate with the induction of impaired metabolic response to insulin.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Potashnik R,Bloch-Damti A,Bashan N,Rudich Adoi
10.1007/s00125-003-1097-5subject
Has Abstractpub_date
2003-05-01 00:00:00pages
639-48issue
5eissn
0012-186Xissn
1432-0428journal_volume
46pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:Both obesity and genetics contribute to cardiovascular disease (CVD). We examined whether a genetic risk score (GRS) prospectively predicted cardiovascular morbidity and mortality among overweight/obese individuals with type 2 diabetes and whether behavioural weight loss could diminish this association....
journal_title:Diabetologia
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00125-015-3610-z
更新日期:2015-08-01 00:00:00
abstract::Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p less than 10(-5)) with relative risk 7.7 and...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00277317
更新日期:1987-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4222-6
更新日期:2017-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:The receptor tyrosine kinase, c-Kit, and its ligand, stem cell factor, control a variety of cellular processes, including pancreatic beta cell survival and differentiation as revealed in c-Kit ( Wv ) mice, which have a p...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2566-5
更新日期:2012-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Gestational diabetes mellitus is a heterogeneous disorder characterised by impaired insulin secretion and action. Our aim was to study whether autoimmunity, variations in genes affecting insulin secretion and action, or both, contribute to the development of gestational diabetes and whether the pathogen...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1388-5
更新日期:2004-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:Abnormal serum IGF-1 levels are associated with an increased risk of type 2 diabetes and cardiovascular disease. However, the causal role of IGF-1 levels within the normal range in cardiometabolic disease remains unclear. We employed Mendelian randomisation to explore the associations between geneticall...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05190-9
更新日期:2020-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:Statins and niacin (nicotinic acid) reduce circulating LDL-cholesterol (LDL-C) levels by different mechanisms. Yet, both increase the risk of diabetes mellitus. Our objective was to relate blood LDL-C concentrations and a genetic risk score (GRS) for LDL-C to the risk of incident diabetes in individuals...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3762-x
更新日期:2015-12-01 00:00:00
abstract::The incidence, prevalence, and ages and dates of onset of diabetes, were studied in 184 families with 2 or more affected children. Results suggested that the siblings of children who developed diabetes before the age of 16 years were 26 times more likely to develop diabetes than other children. Of all siblings surveye...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00280517
更新日期:1980-10-01 00:00:00
abstract::The mechanisms which underlie the development of Charcot joints and foot ulceration are poorly understood. The present study using non-invasive Doppler techniques demonstrates that in the neuropathic leg, the arteries are rigid, peripheral blood flow is increased and associated with arteriovenous shunting. We studied ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00253862
更新日期:1982-01-01 00:00:00
abstract::A representative sample (n = 2140) of the Israeli Jewish population aged 40-70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past bo...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00456115
更新日期:1986-02-01 00:00:00
abstract::Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01223020
更新日期:1978-05-01 00:00:00
abstract::The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 Eu...
journal_title:Diabetologia
pub_type: 杂志文章,多中心研究
doi:10.1007/s001250050736
更新日期:1997-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:We quantified the effect of ADRA2A (encoding α-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies. METHODS:Genotype data for ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 were analysed in >17,000 individuals (1,307 type 2 di...
journal_title:Diabetologia
pub_type: 杂志文章,meta分析
doi:10.1007/s00125-011-2108-6
更新日期:2011-07-01 00:00:00
abstract::The binding of 125I-labelled insulin to human adipocytes was studied at 37 degrees C. The precipitability of the 125I-labelled insulin preparation (0.03 nmol/l) in trichloroacetic acid and the concentration of biologically active insulin (7.5 nmol/l) remained constant in buffer incubated with human adipocytes (100 mic...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01236312
更新日期:1977-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:As one of the key adipokines, retinol binding protein 4 (RBP4) is suggested to positively correlate with insulin resistance; however, not all clinical studies support this association. Although some explanations are proposed for this discrepancy, the temporal aspect of RBP4 secretion has not been consid...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3807-1
更新日期:2016-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Despite recent advances, our understanding of its pathophysiology remains incomplete. The aim of this study was to provide deeper insight into the complex network of molecular and cellular c...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05218-0
更新日期:2020-10-01 00:00:00
abstract::We describe a patient who had an anaphylactic reaction to highly purified pork insulin; he was not allergic however to beef insulin. The sensitivity to pork but not to beef insulin was confirmed by skin testing, radioallergosorbent test (RAST) and RAST inhibition. A scheme is suggested for the investigation of such pa...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00253575
更新日期:1982-05-01 00:00:00
abstract::The physiologically predominant signal for pancreatic beta cells to secrete insulin is glucose. While circulating glucose levels and beta cell glucose metabolism regulate the amount of released insulin, additional signals emanating from other tissues and from neighbouring islet endocrine cells modulate beta cell funct...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-015-3862-7
更新日期:2016-04-01 00:00:00
abstract::Plasma insulin, intact proinsulin and 32-33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF02342446
更新日期:1992-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. METHODS:Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I),...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051197
更新日期:1999-05-01 00:00:00
abstract::We studied the effect of chronic exposure to high glucose on the glucose transport regulation in hamster pancreatic Beta cells in permanent culture (HIT). Cells were exposed to either 5.5 mmol/l or 16.7 mmol/l glucose for 48 h and then glucose transport was studied by measuring the (3H)-2-deoxyglucose uptake for 5 and...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00405011
更新日期:1991-05-01 00:00:00
abstract:AIMS/HYPOTHESIS:Interleukin-1beta is a putative mediator of pancreatic beta-cell dysfunction and damage in Type I (insulin-dependent) diabetes mellitus. To better understand the molecular mechanisms involved in IL-1beta effects, we carried out a differential display of mRNA by RT-PCR to identify novel cytokine-regulate...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051292
更新日期:1999-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Despite the overlap in occurrence of cardiovascular disease (CVD) and type 2 diabetes and their risk factors, family history of these diseases has not yet been investigated simultaneously in relation to cardiometabolic markers in offspring. We examined how a family history of CVD and/or diabetes relates...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-016-3988-2
更新日期:2016-08-01 00:00:00
abstract::The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU.kg body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 con...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050519
更新日期:1996-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. METHODS:MEDLINE, EMBASE and the Cochrane L...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-020-05295-1
更新日期:2021-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Thickening of the basement membrane and selective loss of pericytes occur early in diabetic retinopathy. As we showed previously that pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations, we aimed to verify if altered adhesion could influence ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-003-1043-6
更新日期:2003-03-01 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: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:AIMS/HYPOTHESIS:Progressive decline in functional beta cell mass is central to the development of type 2 diabetes. Elevated serum levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) are associated with beta cell failure in type 2 diabetes and eNAMPT immuno-neutralisation improves glucose tolerance i...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-019-05029-y
更新日期:2020-02-01 00:00:00
abstract::A controlled trial of oral nicotinamide to prevent the onset of diabetes mellitus in high risk children was conducted in two centres. The selection criteria were age less than 16 years, islet cell antibody greater than or equal to 80 IUs, and first phase insulin release less than 5th percentile. All of eight untreated...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/BF00405010
更新日期:1991-05-01 00:00:00