Abstract:
:Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). We have developed a simple, reproducible, and quantitative immunoprecipitation radioligand assay using as antigen in vitro transcribed and translated [35S]methionine-labeled human islet GAD65. By using this assay, 77% (77 of 100) of serum samples from recent-onset IDDM patients were positive for GAD65 antibodies compared with 4% (4 of 100) of serum samples from healthy control subjects. In competition analysis with unlabeled purified recombinant human islet GAD65, binding to tracer was inhibited in 74% (74 of 100) of the GAD65-positive IDDM serum samples compared with 2% of the control samples. The levels of GAD antibodies expressed as an index value relative to a standard serum, analyzed with or without competition, were almost identical (r = 0.991). The intra- and interassay variations of a positive control serum sample were 2.9 and 7.6%, respectively (n = 4). The frequency of GAD antibodies was significantly higher with IDDM onset before the age of 30 (80%, 59 of 74) than after the age of 30 (48%, 10 of 21) (P < 0.01). The prevalence of islet cell antibodies showed a similar pattern relative to age at onset. Because simultaneous occurrences of multiple autoimmune phenomena are common, we analyzed sera from patients with other autoimmune diseases. The frequency of GAD antibodies in sera positive for DNA autoantibodies (8% [2 of 25] and 4% [1 of 25] in competition analysis) or rheuma factor autoantibodies [12% (4 of 35) and 3% (1 of 35) in competition analysis] was not different from that in control samples. In contrast, in sera positive for ribonucleoprotein antibodies the frequency of GAD antibodies was significantly increased (73% [51 of 70] and 10% [7 of 70] in competition analysis [P < 0.025]). In conclusion, even large numbers of serum samples can now be tested for GAD65 antibodies in a relatively short time, allowing screening of individuals without a family history of IDDM for the presence of this marker.
journal_name
Diabetesjournal_title
Diabetesauthors
Petersen JS,Hejnaes KR,Moody A,Karlsen AE,Marshall MO,Høier-Madsen M,Boel E,Michelsen BK,Dyrberg Tdoi
10.2337/diab.43.3.459subject
Has Abstractpub_date
1994-03-01 00:00:00pages
459-67issue
3eissn
0012-1797issn
1939-327Xjournal_volume
43pub_type
杂志文章相关文献
DIABETES文献大全abstract::The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the ti...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.12.1180
更新日期:1984-12-01 00:00:00
abstract::The preferential channeling of different fuels to fat and changes in the transcription profile of adipose tissue and skeletal muscle are poorly understood processes involved in the pathogenesis of obesity and insulin resistance. Carbohydrate and lipid metabolism may play relevant roles in this context. Freely moving l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.3.601
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVE:Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impac...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0320
更新日期:2010-11-01 00:00:00
abstract::Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). However, long-term inhibition of PARP, an enzyme involved in DNA repair, can potentially result in premature aging, loss of genome stability, and other side ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1514
更新日期:2005-05-01 00:00:00
abstract::The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.53.6.1614
更新日期:2004-06-01 00:00:00
abstract::Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.5.449
更新日期:1982-05-01 00:00:00
abstract::The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SI(Clamp)) that is better than that of many other surrogate indexes. However, correlation between a surrogate and reference standard may improve as variability between subj...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.7.1914
更新日期:2005-07-01 00:00:00
abstract::Hypogonadotropism is a common feature of uncontrolled diabetes, for which the ultimate mechanism remains to be elucidated. Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as major gatekeepers of the gonadotropic axis. Alteration in the hypothalamic KiSS-1...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-1584
更新日期:2006-09-01 00:00:00
abstract::Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent o...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.38.12.1512
更新日期:1989-12-01 00:00:00
abstract:OBJECTIVE:The aim of the current study was to evaluate the long-term effects of leptin on glucose metabolism, diabetes complications, and life span in an insulin-dependent diabetes model, the Akita mouse. RESEARCH DESIGN AND METHODS:We cross-mated Akita mice with leptin-expressing transgenic (LepTg) mice to produce Ak...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1795
更新日期:2011-09-01 00:00:00
abstract::Selective peroxisome proliferator-activated receptor (PPAR) gamma modulation is a new pharmacological approach that, based on selective receptor-cofactor interactions and target gene regulation, should result in potent insulin sensitization in the absence of PPARgamma-mediated adverse effects. Here, we characterize tw...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.12.3442
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subseq...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1578
更新日期:2008-02-01 00:00:00
abstract::Previous studies have indicated that individuals with type 2 diabetes have an increased resting metabolic rate (RMR) but decreased insulin-induced thermogenesis (IIT) compared with those with normal glucose tolerance (NGT). When and by which mechanisms these abnormalities occur during the development of diabetes remai...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.8.1607
更新日期:1999-08-01 00:00:00
abstract::A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated wi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.1.88
更新日期:1983-01-01 00:00:00
abstract::Recently, peptides with opioid-like activity have been demonstrated in peptic digests of dietary protein. The present study was designed to determine the effect of digested and undigested gluten on postprandial insulin and glucagon levels in conscious dogs. The intragastric instillation of digested gluten (25 g) elici...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.4.362
更新日期:1981-04-01 00:00:00
abstract::The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP-sensitive K+ channels. It is an ATP-binding cassette protein comprising 17 transmembrane helices. SUR is endowed with binding sites for channel blockers like the antidiabetic sulfonylurea glibenclamide and for the chemically very heterogeneous ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.suppl_3.s128
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:This study aimed to estimate the current cumulative risk of end-stage renal disease (ESRD) due to diabetic nephropathy in a large, nationwide, population-based prospective type 1 diabetes cohort and specifically study the effects of sex and age at onset. RESEARCH DESIGN AND METHODS:In Sweden, all incident ca...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1744
更新日期:2010-07-01 00:00:00
abstract::Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and the His-Gly dipeptide motif, has provided a previously unannotated gene that is indu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-0585
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:High-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by at...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1278
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVE:ob/ob and db/db mice manifest myocardial hypertrophy, insulin resistance, altered substrate utilization, mitochondrial dysfunction, and lipid accumulation. This study was designed to determine the contribution of central and peripheral leptin signaling to myocardial metabolism and function in ob/ob and db/db ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1106
更新日期:2011-05-01 00:00:00
abstract::The interaction between insulin and its receptor was investigated using both monoclonal and polyclonal anti-insulin antibodies. After covalent cross-linking of 125I-insulin to the insulin receptor on cultured human lymphocytes (IM-9 cells) using disuccinimidyl suberate, we inquired whether the insulin-receptor complex...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.33.8.778
更新日期:1984-08-01 00:00:00
abstract::Different degrees of beta-cell failure and apoptosis are present in type 1 and type 2 diabetes. It has been recently suggested that high glucose-induced beta-cell apoptosis in type 2 diabetes shares a final common pathway with type 1 diabetes, involving interleukin-1beta (IL-1beta) production by beta-cells, nuclear fa...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.11.3238
更新日期:2005-11-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is a potent glucose-lowering agent of potential interest for the treatment of type 2 diabetes. To evaluate actions of NN2211, a long-acting GLP-1 derivative, we examined 11 patients with type 2 diabetes, age 59 +/- 7 years (mean +/- SD), BMI 28.9 +/- 3.0 kg/m(2), HbA(1c) 6.5 +/- 0.6%, i...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.51.2.424
更新日期:2002-02-01 00:00:00
abstract::Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.5.1588
更新日期:2002-05-01 00:00:00
abstract::Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1459
更新日期:2014-09-01 00:00:00
abstract::An A-to-G transition in the mitochondrial tRNALeu(UUR) gene at base pair 3243 has been shown to be associated with the maternally transmitted clinical phenotype of NIDDM and sensorineural hearing loss in white and Japanese pedigrees. We have detected this mutation in 25 of 50 tested members of five white French pedigr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.4.478
更新日期:1996-04-01 00:00:00
abstract::Women gain weight and their diabetes risk increases as they transition through menopause; these changes can be partly reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1342
更新日期:2018-08-01 00:00:00
abstract::This article presents a model for the HLA effect in insulin-dependent diabetes mellitus (IDDM) that is almost the mirror image of a model suggested by Nepom. In the Nepom model, the products of certain HLA alleles are associated with IDDM because they bind and present a specific peptide or peptides so as to induce an ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.41.2.123
更新日期:1992-02-01 00:00:00
abstract:OBJECTIVE:Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes, the myocardium relies heavily on fatty acid metabolism for energy. Whether conditions that affect myocardial glucose use and fatty acid utilization,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1199
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db09-0699
更新日期:2010-09-01 00:00:00