Abstract：
AIMS/HYPOTHESIS:The stress-activated nuclear protein transcription regulator 1 (NUPR1) is induced in response to glucose and TNF-α, both of which are elevated in type 2 diabetes, and Nupr1 has been implicated in cell proliferation and apoptosis cascades. We used Nupr1(-/-) mice to study the role of Nupr1 in glucose homeostasis under normal conditions and following maintenance on a high-fat diet (HFD). METHODS:Glucose homeostasis in vivo was determined by measuring glucose tolerance, insulin sensitivity and insulin secretion. Islet number, morphology and beta cell area were assessed by immunofluorescence and morphometric analysis, and islet cell proliferation was quantified by analysis of BrdU incorporation. Islet gene expression was measured by gene arrays and quantitative RT-PCR, and gene promoter activities were monitored by measuring luciferase activity. RESULTS:Nupr1(-/-) mice had increased beta cell mass as a consequence of enhanced islet cell proliferation. Nupr1-dependent suppression of beta cell Ccna2 and Tcf19 promoter activities was identified as a mechanism through which Nupr1 may regulate beta cell cycle progression. Nupr1(-/-) mice maintained on a normal diet were mildly insulin resistant, but were normoglycaemic with normal glucose tolerance because of compensatory increases in basal and glucose-induced insulin secretion. Nupr1 deletion was protective against HFD-induced obesity, insulin resistance and glucose intolerance. CONCLUSIONS/INTERPRETATION:Inhibition of NUPR1 expression or activity has the potential to protect against the metabolic defects associated with obesity and type 2 diabetes.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Barbosa-Sampaio HC,Liu B,Drynda R,Rodriguez de Ledesma AM,King AJ,Bowe JE,Malicet C,Iovanna JL,Jones PM,Persaud SJ,Muller DSdoi
10.1007/s00125-013-3006-xsubject
Has Abstractpub_date
2013-11-01 00:00:00pages
2477-86issue
11eissn
0012-186Xissn
1432-0428journal_volume
56pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract：:The plasma concentration of 1,5-anhydro-D-glucitol(AG)(1-deoxyglucose) is known to decrease in diabetic patients. In order to evaluate the usefulness of this polyol as a diabetic marker, we examined the specificity of the plasma AG reduction in various diseases: the plasma AG level was determined in 108 newly diagnose...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00279131
更新日期：1988-01-01 00:00:00
abstract：AIMS/HYPOTHESIS:The newly identified liver- and fat-derived hormone, betatrophin, has recently been linked to insulin resistance and pancreatic beta cell growth in mice. These preclinical findings have suggested betatrophin as a potential candidate for novel glucose-lowering treatment concepts involving beta cell regen...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-014-3208-x
更新日期：2014-06-01 00:00:00
abstract：:Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between p...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00399934
更新日期：1992-09-01 00:00:00
abstract：:We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence or development of IDDM. Among t...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250050578
更新日期：1996-11-01 00:00:00
abstract：:A potent high-titre glucagon antibody pool was used to induce a state of acute glucagon deficiency in order to investigate the importance of glucagon in maintaining euglycaemia in the fed and fasted anaesthetised rat. Binding characteristics of the antiserum and evidence of its neutralisation of the biological effects...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00280887
更新日期：1985-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:Maternal Type I (insulin-dependent) diabetes mellitus is associated with an increased risk for fetal malformations and spontaneous abortions. Although the pathogenic mechanism is not fully understood, reactive oxygen species have been shown to contribute to the pathogenesis in experimental studies. By m...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051686
更新日期：2001-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance. METHODS:This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-012-2533-1
更新日期：2012-06-01 00:00:00
abstract：:The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matri...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250050785
更新日期：1997-09-01 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:The study was designed to identify the key metabolic signals of glucose-stimulated proinsulin gene transcription and translation, focusing on the mechanism of succinate stimulation of insulin production. METHODS:Wistar rat islets were incubated in 3.3 mmol/l glucose with and without esters of different...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-005-1811-6
更新日期：2005-08-01 00:00:00
abstract：AIMS/HYPOTHESIS:A common G to A polymorphism ( UCSNP-43) in the Calpain 10 gene was recently found to be associated with Type II (non-insulin-dependent) diabetes mellitus and variations in post-absorptive and insulin stimulated glucose metabolism in vivo. We aimed to study the influence of Calpain 10 polymorphism on in...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-001-0732-2
更新日期：2002-02-01 00:00:00
abstract：:For many, the extent to which blood glucose control can be lowered is limited by risk of hypoglycaemia. Hypoglycaemia is feared and carries fiscal, social and medical costs, with risk of death being associated with severe hypoglycaemia in patients with type 2 diabetes at high cardiovascular risk. In this issue of Diab...
journal_title：Diabetologia
pub_type： 评论,杂志文章
doi：10.1007/s00125-015-3550-7
更新日期：2015-06-01 00:00:00
abstract：:The global nutrition transition, which embraces major changes in how food is produced, distributed and consumed, is associated with rapid increases in the prevalence of obesity, but the implications for diabetes differ between populations. A simple conceptual model treats diabetes risk as the function of two interacti...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-019-4944-8
更新日期：2019-10-01 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：:The aim of the present study was to elucidate the pathophysiologic significance of circulating ouabain as a link between insulin resistance (IR) and hypertension (HT) in NIDDM. Euglycaemic (4.5 mmol/l) hyperinsulinaemic (360-580 pmol/l) clamping was performed using an artificial endocrine pancreas. Plasma ouabain-like...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250050354
更新日期：1995-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:We investigated of the effects of fatty acid composition of the maternal diet on fetal and postnatal growth, morphology of the pancreas and glucose metabolism and muscle hexosamine concentrations in the adult offspring of rats. METHODS:High-fat diets enriched with either saturated or unsaturated fatty ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-002-0918-2
更新日期：2002-10-01 00:00:00
abstract：AIMS/HYPOTHESIS:We assessed secular trends of cardiovascular outcomes following first diagnosis of myocardial infarction (MI) or diabetes in an unselected population. METHODS:All Danish residents aged > or = 30 years without prior diabetes or MI were identified by individual-level linkage of nationwide registers. Indi...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-010-1783-z
更新日期：2010-08-01 00:00:00
abstract：:Mild hypoglycaemia was induced using an artificial pancreas in five normal subjects (from 5.00 +/- 0.15 to 2.83 +/- 0.15 mmol/l) by infusing 28 mU/m2 per min soluble insulin for 60 min. Six Type 1 (insulin-dependent) diabetic patients were stabilized for 14h using an artificial pancreas. They were then rendered hypogl...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00254837
更新日期：1982-02-01 00:00:00
abstract：AIMS/HYPOTHESIS:Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a risk marker for CVD and has pro-inflammatory effects...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-010-1969-4
更新日期：2011-02-01 00:00:00
abstract：AIMS/HYPOTHESIS:Serum potassium has been found to be a significant predictor of diabetes risk, but the effect of dietary potassium on diabetes risk is not clear. We sought to determine if dietary potassium is associated with risk of incident type 2 diabetes in young adults. METHODS:We used data from the Coronary Arter...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-012-2487-3
更新日期：2012-05-01 00:00:00
abstract：:The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pa...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-015-3828-9
更新日期：2016-03-01 00:00:00
abstract：:Insulin resistance of the skeletal muscle plays a key role in the development of the metabolic endocrine syndrome and its further progression to non-insulin dependent diabetes (NIDDM). Available data suggest that insulin resistance is caused by an impaired signal from the insulin receptor to the glucose transport syst...
journal_title：Diabetologia
pub_type： 传,历史文章,杂志文章,评审
doi：10.1007/BF00400838
更新日期：1994-09-01 00:00:00
abstract：:A double HbA1c-band was demonstrated in isoelectric focussing of blood from diabetics with a fasting blood glucose above 11 mmol/l. The same band-doubling was also demonstrated after incubation of erythrocytes in glucose/saline solutions. This finding may reflect the presence of the initial condensation product betwee...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00281827
更新日期：1980-11-01 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：:The insulin receptor substrate proteins IRS1 and IRS2 are key targets of the insulin receptor tyrosine kinase and are required for hormonal control of metabolism. Tissues from insulin-resistant and diabetic humans exhibit defects in IRS-dependent signalling, implicating their dysregulation in the initiation and progre...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-012-2644-8
更新日期：2012-10-01 00:00:00
abstract：:Three members of the angiopoietin-like (ANGPTL) family of proteins, ANGPTL3, ANGPTL4 and ANGPTL8, are known regulators of plasma triacylglycerol levels. Recently, these three proteins have garnered considerable interest as potential targets for therapeutically reducing plasma triacylglycerol levels and improving cardi...
journal_title：Diabetologia
pub_type： 评论,杂志文章
doi：10.1007/s00125-018-4604-4
更新日期：2018-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:We aimed to assess whether persistence of C-peptide secretion is associated with less glucose variability and fewer low-glucose events in adults with type 1 diabetes who use flash monitoring. METHODS:We performed a cross-sectional study of 290 adults attending a university teaching hospital diabetes cl...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-020-05099-3
更新日期：2020-05-01 00:00:00
abstract：:The NOD mouse, which shows many features of human IDDM, is extensively used to evaluate the role of T lymphocytes in the pathogenesis of autoimmune diabetes. The development of diabetes in this model appears to be controlled by a finely tuned immunoregulatory balance between autoaggressive T cells and regulatory immun...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00408468
更新日期：1994-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:This long-term study was designed to further characterise the retinal safety profile of insulin glargine and human neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus. METHODS:An open-label, 5 year, randomised (1:1), multicentre, stratified, parallel-group study conducted...
journal_title：Diabetologia
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s00125-009-1415-7
更新日期：2009-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:Neurogenin 3 (NEUROG3), a basic helix-loop-helix transcription factor that is needed for endocrine cell development in the embryonic pancreas, has been shown to induce transdifferentiation of duct cells from adult pancreas towards a neuro-endocrine phenotype. Our study explored the endocrine transdiffer...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-006-0299-z
更新日期：2006-08-01 00:00:00
