Abstract:
AIMS/HYPOTHESIS:The cyclooxygenase-2 (PTGS2, previously known as COX2) enzyme and its products, such as prostaglandin E(2) (PGE(2)), have been implicated in the pathogenesis of several inflammatory diseases including islet dysfunction under diabetic conditions. In this study we evaluated whether diabetic conditions in vitro, such as high-glucose (HG) culture or AGE, or in vivo in animal models of diabetes can induce PTGS2 expression and activity in pancreatic islets. MATERIALS AND METHODS:Isolated human pancreatic islets were treated for 24 h with HG (25 mmol/l) or with S100b (5 mg/l), a specific ligand for the AGE-specific receptor. PTGS2 and cyclooxygenase-1 (PTGS1, previously known as COX1) mRNA, protein expression and product PGE(2) were analysed by RT-PCR, Western blots and specific enzyme immunoassay respectively. Islet PTGS2 production in animal models was assessed by immunofluorescence. RESULTS:Treatment of human pancreatic islets with HG and S100b led to a three-five-fold induction of PTGS2 mRNA (p<0.001). PTGS2 protein and its product PGE(2) (351.4+/-13.05 fg/ml vs control 39.4+/-0.11 fg/ml) were also increased (p<0.001). Pretreatment with specific inhibitors demonstrated the involvement of protein kinase C and oxidant stress in S100b- and HG-induced PTGS2 expression. However, insulin secretion was not significantly altered by S100b. Double immunofluorescent staining showed increased PTGS2 production in pancreatic islets from diabetic mice relative to corresponding controls. CONCLUSION/INTERPRETATION:These results show for the first time that diabetes as well as diabetic conditions such as AGE and HG in vitro can directly upregulate the expression of the inflammatory PTGS2 gene in pancreatic islets. This might contribute to the pathogenesis of islet dysfunction in diabetes.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Shanmugam N,Todorov IT,Nair I,Omori K,Reddy MA,Natarajan Rdoi
10.1007/s00125-005-0065-7subject
Has Abstractpub_date
2006-01-01 00:00:00pages
100-7issue
1eissn
0012-186Xissn
1432-0428journal_volume
49pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract::IDDM is associated with an increase in kidney size, which is due to cellular hypertrophy and progressive matrix accumulation within the glomerulus and throughout the tubulo-interstitium. The present study addressed the potential role of cysteine and metalloproteinases in renal hypertrophy of short-term diabetes. Three...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403374
更新日期:1994-06-01 00:00:00
abstract::Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU m2-1.min-1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7 +/- 0.3 vs 4.4 +/- 0.2 mmol/l) was similar in the two groups, whereas hepat...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00404801
更新日期:1990-04-01 00:00:00
abstract:AIMS/HYPOTHESIS:To investigate the pathways by which cyclic AMP (cAMP) stimulates glucagon-like peptide-1 (GLP-1) secretion, using the GLUTag enteroendocrine cell line. MATERIALS AND METHODS:GLP-1 release from GLUTag cells was measured in response to agents that increase cAMP, and single cells were studied by fluoresc...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0750-9
更新日期:2007-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Recent genome-wide association studies have suggested that a polymorphism in GCKR, the gene encoding the glucokinase regulatory protein, is involved in triacylglycerol regulation. Our aim was to examine in large-scale studies the common GCKR rs780094 polymorphism in relation to metabolic traits (mainly ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0865-z
更新日期:2008-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Differences in seasonality of birth patterns between the general population and the group who develop Type I (insulin-dependent) diabetes mellitus indicate that environmental factors operating around the antenatal and perinatal period could be important. We investigated whether the same unsual patterns ...
journal_title:Diabetologia
pub_type: 杂志文章,多中心研究
doi:10.1007/pl00002957
更新日期:2001-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Paraoxonase is a member of a multigene family of three genes. Paraoxonase2 gene polymorphisms have been associated with coronary heart disease in non-diabetic patients and with an increased fasting glycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus. We tested the hypothesis of ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051586
更新日期:2001-01-01 00:00:00
abstract::In healthy subjects hypoglycaemia causes a fall in body temperature through increased sweating and limb blood flow, and despite increased metabolic heat production. We studied thermoregulatory responses to hyperinsulinaemic (100 mU.m-2.min-1) (a) hypoglycaemia (2.5 mmol/l) and (b) euglycaemia (4.5 mmol/l) in insulin-d...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00417693
更新日期:1994-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial. METHODS:In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m2), we measured VAT and subcutaneous ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1891-3
更新日期:2005-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes. Recent genome-wide association (GWA) studies have identified multiple loci robustly associated with BMI and risk of obesity. However, information on their associations with type 2 diabetes is limited. Such information could help increase our understand...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2044-5
更新日期:2011-04-01 00:00:00
abstract::A series of recent experimental findings are reviewed to indicate that glucokinase does not represent the pancreatic B-cell glucoreceptor. Whether in liver, pancreatic islet or insulin-producing tumoral cell homogenates, glucokinase fails to yield a higher reaction velocity with alpha-than beta-D-glucose. At a high gl...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00281986
更新日期:1985-08-01 00:00:00
abstract::There is ample evidence that environmental factors are involved in the aetiology of type 1 diabetes, but the nature and timing of the interactions are poorly understood. The intrauterine environment is known to play a role in the later development of type 2 diabetes, and this review considers a possible role in type 1...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-013-2929-6
更新日期:2013-09-01 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:Aggregation of islet amyloid polypeptide (IAPP) to form amyloid contributes to beta cell dysfunction in type 2 diabetes. Human but not non-amyloidogenic rodent IAPP induces islet macrophage proIL-1β synthesis. We evaluated the effect of IL-1 receptor antagonist (IL-1Ra) on islet inflammation and dysfunc...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3447-x
更新日期:2015-03-01 00:00:00
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::Isolated pancreatic islets of normoglycemic sand rats do not respond to 2.5 mM glucose with an enhanced glucagon secretion, which could be observed in normal Wistar rats. Arginine stimulates glucagon release in the presence of 2.5 mM glucose in Wistar rats as well as in sand rats. The secretion pattern is not caused b...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00422820
更新日期:1975-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetes increases the risk of premature death and reduces work productivity. We estimated the impact of diabetes in China in terms of mortality, years of life lost, and productivity-adjusted life years (PALYs) lost in the Chinese population. METHODS:Life table modelling was used with simulated follow-...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-019-4875-4
更新日期:2019-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetic distal symmetrical sensory polyneuropathy (DSP) affects 20-30% of diabetic patients. Transcutaneous electrical nerve stimulation (TENS) and electrical spinal cord stimulation have been proposed as physical therapies. We performed a controlled, randomised pilot trial to compare the effects of hi...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00125-005-1728-0
更新日期:2005-05-01 00:00:00
abstract::Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403907
更新日期:1996-08-01 00:00:00
abstract::Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n = 16) with albumin excretion ranging between 1...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00262209
更新日期:1984-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to investigate the action of the glucose-lowering compound sodium tungstate on glucose transport in muscle myotubes and to unravel the molecular events underlying the effects observed. METHODS:We studied the effects of tungstate on 2-deoxy-D: -glucose uptake, levels and transl...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-008-1003-2
更新日期:2008-07-01 00:00:00
abstract:UNLABELLED:AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiov...
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/s001250051229
更新日期:1999-07-01 00:00:00
abstract::Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/l of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00423150
更新日期:1979-01-01 00:00:00
abstract::Diabetic patients exhibit a higher incidence of post-surgical sepsis, as well as a higher rate of mortality from sepsis, than their non-diabetic counterparts. This may be a result of cardiovascular deterioration associated with diabetes mellitus. This study was designed to characterize the cardiovascular sequelae asso...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00401512
更新日期:1991-10-01 00:00:00
abstract::Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/BF00252649
更新日期:1981-09-01 00:00:00
abstract::Families (n = 14) with more than 1 sibling with insulin dependent diabetes were matched with families of similar size and age distribution containing only 1 affected child. The distribution of HLA haplotypes, age of onset of disease, and seasonal onset of disease were compared in the two groups. The data are not consi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00421852
更新日期:1980-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Clinical trials are in progress to test thiazolidinediones in neurodegenerative diseases such as Alzheimer's disease that involve deficiencies in brain glucose metabolism. While thiazolidinediones enhance glucose uptake in non-cerebral tissues, their impact on brain energy metabolism has not been invest...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0326-0
更新日期:2006-09-01 00:00:00
abstract::An inconsistency has come to light between the conclusion of Lucassen et al. that IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS) locus and their own data showing statistically significant associations between insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403307
更新日期:1996-05-01 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::The aim of this study was to compare the causes of death and parameters related to alcohol consumption, between subjects diagnosed as diabetic, clinically by their general practitioner, or glucose intolerant and in particular as diabetic, using the epidemiological criteria of an abnormal glucose level following an ora...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400850
更新日期:1992-01-01 00:00:00
abstract::Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on va...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00280892
更新日期:1985-07-01 00:00:00