Abstract:
OBJECTIVE:Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, both diabetic and nondiabetic, and control subjects) and/or disease progression (differences between diabetic and nondiabetic twins). RESEARCH DESIGN AND METHODS:We studied patterns of inflammatory gene expression in peripheral blood monocytes of MZ twin pairs (n = 10 pairs) discordant for childhood-onset type 1 diabetes, normal control twin pairs (n = 10 pairs), and healthy control subjects (n = 51) using quantitative-PCR (Q-PCR). We tested the 24 genes previously observed by whole genome analyses and verified by Q-PCR in autoimmune diabetes and performed a hierarchical cluster analysis. RESULTS:Of 24 genes abnormally expressed in childhood-onset type 1 diabetes, we revalidated abnormal expression in 16 of them in diabetic twins including distinct sets of downregulated (P < 0.03) and upregulated (P < 0.02) genes. Of these 16 genes, 13 were abnormally expressed in nondiabetic twins, implicating these genes in diabetes susceptibility (P < 0.044 for all). Cluster analysis of monocyte gene-expression in nondiabetic twins identified two distinct, mutually exclusive clusters, while diabetic twins had a network of positively correlated genes. CONCLUSIONS:Patients with childhood-onset type 1 diabetes show abnormal monocyte gene-expression levels with an altered gene-expression network due to gene-environment interaction. Importantly, perturbed gene-expression clusters were also detected in nondiabetic twins, implicating monocyte abnormalities in susceptibility to diabetes.
journal_name
Diabetesjournal_title
Diabetesauthors
Beyan H,Drexhage RC,van der Heul Nieuwenhuijsen L,de Wit H,Padmos RC,Schloot NC,Drexhage HA,Leslie RDdoi
10.2337/db09-1433subject
Has Abstractpub_date
2010-07-01 00:00:00pages
1751-5issue
7eissn
0012-1797issn
1939-327Xpii
db09-1433journal_volume
59pub_type
杂志文章相关文献
DIABETES文献大全abstract::Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.5.972
更新日期:2001-05-01 00:00:00
abstract::A total of 32 pairs of obese fathers or mothers and their obese offsprings, aged 20 yr or younger, from 25 families with established hyperinsulinemic obesity aged 11-20 yr equally showed an insulin hyperresponse to glucose, the offspring 10 yr or younger revealed a rather normal insulin response, despite the presence ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.1.14
更新日期:1981-01-01 00:00:00
abstract::Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a fas...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.1.251
更新日期:2002-01-01 00:00:00
abstract::We have recently reported an A to G transition at nucleotide position 3243 in the mitochondrial DNA (mtDNA) tRNA(Leu(UUR)) gene in a large family with non-insulin-dependent diabetes mellitus (NIDDM). Characteristic was its maternal transmission and an associated sensorineural hearing loss. In a screening of a Dutch an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.6.746
更新日期:1994-06-01 00:00:00
abstract::We tested the hypothesis that green tea prevents diabetes-related tissue dysfunctions attributable to oxidation. Diabetic rats were treated daily with tap water, vitamins C and E, or fresh Japanese green tea extract. After 12 months, body weights were decreased, whereas glycated lysine in aorta, tendon, and plasma wer...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.2.517
更新日期:2005-02-01 00:00:00
abstract::Recent studies have shown that two different voltage-dependent Ca2+ channels are expressed in pancreatic islets, the beta-cell/neuroendocrine-brain and the cardiac subtypes. The effects of chronic hyperglycemia on the levels in pancreatic islets of the mRNAs encoding the alpha 1-subunits of the beta-cell and cardiac s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.7.948
更新日期:1993-07-01 00:00:00
abstract::The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its me...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究
doi:10.2337/diabetes.51.8.2629
更新日期:2002-08-01 00:00:00
abstract::The molecular underpinnings of β-cell dysfunction and death leading to diabetes are not fully elucidated. The objective of the current study was to investigate the role of endoplasmic reticulum-associated degradation (ERAD) in pancreatic β-cells. Chemically induced ERAD deficiency in the rat insulinoma cell line INS-1...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0624
更新日期:2019-04-01 00:00:00
abstract::Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.6.862
更新日期:1993-06-01 00:00:00
abstract::Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic beta-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca2+ concentration) ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.8.1942
更新日期:2004-08-01 00:00:00
abstract::To determine whether nonglucose nutrient-induced insulin secretion is impaired in pre-diabetes, subjects with impaired or normal fasting glucose were studied after ingesting either a mixed meal containing 75 g glucose or 75 g glucose alone. Despite comparable glucose areas above basal, glucose-induced insulin secretio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1272
更新日期:2007-04-01 00:00:00
abstract::To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.1.80
更新日期:1987-01-01 00:00:00
abstract::Dynamic aspects of whole body alanine and glycine metabolism have been explored in insulin-dependent (type I) diabetic subjects. Using a primed, continuous intravenous (i.v.) infusion of [2H3]alanine and [15N]glycine given simultaneously with [1-13C]leucine, whole body alanine and glycine fluxes and their rates of de ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.1.67
更新日期:1985-01-01 00:00:00
abstract::GLUT4 is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine whether GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by u...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1075
更新日期:2017-06-01 00:00:00
abstract::C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin be...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0733
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:A major feature of type 1 diabetes is the appearance of islet autoantibodies before diagnosis. However, although the genetics of type 1 diabetes is advanced, the genetics of islet autoantibodies needs further investigation. The primary susceptibility loci in type 1 diabetes, the HLA class I and II genes, are ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0131
更新日期:2011-10-01 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::Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1413
更新日期:2016-08-01 00:00:00
abstract::Compartmentalization of kinases and phosphatases is a key determinant in the specificity of second messenger-mediated signaling events. Localization of the cAMP-dependent protein kinase (PKA) and other signaling enzymes is mediated by interaction with A-kinase anchoring proteins (AKAPs). This study focused on recent a...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.2007.s385
更新日期:2002-12-01 00:00:00
abstract::Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.11.3347
更新日期:2002-11-01 00:00:00
abstract::We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.2.202
更新日期:1992-02-01 00:00:00
abstract::Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.4.763
更新日期:2001-04-01 00:00:00
abstract::A unit was constructed that consisted of a core of hollow fibers through which low-molecular-weight substances, such as glucose and insulin, could pass freely but were impermeable to high-molecular-weight proteins, such as antibodies. Islets of Langerhans from normal rats were planted in the space surrounding the fibe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.12.1136
更新日期:1977-12-01 00:00:00
abstract:OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT)...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/db11-0827
更新日期:2011-12-01 00:00:00
abstract::To elucidate the precise significance of pancreatic A-cell hypersecretion in the pathogenesis of diabetes mellitus, the change in the immunoreactive glucagon (IRG) response to intravenous arginine was studied in both nonobese, hypoinsulinemic non-insulin-dependent (NIDDM) and insulin-dependent diabetic (IDDM) subjects...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.9.762
更新日期:1980-09-01 00:00:00
abstract::Immunosuppressive drugs are routinely used to provide tolerance after whole pancreas and islet cell transplantations. While they are essential in inhibiting graft rejection, little is known about their effect on islet function and beta-cell viability. In this study, we report that tacrolimus, sirolimus, and mycophenol...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.2.424
更新日期:2005-02-01 00:00:00
abstract::Previously studied inhibitors of aldose reductase were largely from two chemical classes, spirosuccinamide/hydantoins and carboxylic acids. Each class has its own drawbacks regarding selectivity, in vivo potency, and human safety; as a result, the pathogenic role of aldose reductase in diabetic retinopathy remains con...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0138
更新日期:2006-10-01 00:00:00
abstract::The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in the regulation and...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0232
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESI...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0585
更新日期:2007-11-01 00:00:00
abstract::Endothelial cells in culture retain many of the functional properties of the endothelium in vivo. At high cell density, they become contact-inhibited. Endothelial cells, like vascular smooth muscle cells and fibroblasts, express binding sites for low density lipoprotein when depleted of sterol. In contact-inhibited en...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.2.s19
更新日期:1981-01-01 00:00:00