Abstract:
OBJECTIVE:In humans, it is unclear if insulin resistance at the monocyte level is associated with atherosclerosis in vivo. Here we have studied first-degree relatives of patients with type 2 diabetes to investigate whether a reduction in components of the insulin signal transduction pathways, such as the insulin receptor (InsR) or InsR substrate 1 or 2 (IRS1 or IRS2), or a reduction in genetic modifiers of insulin action, such as the TIMP3/ADAM17 (tissue inhibitor of metalloproteinase 3/A disintegrin and metalloprotease domain 17) pathway, is associated with evidence of atherosclerosis. RESEARCH DESIGN AND METHODS:Insulin sensitivity was analyzed through euglycemic-hyperinsulinemic clamp, and subclinical atherosclerosis was analyzed through intimal medial thickness. Monocytes were isolated through magnetic cell sorting, and mRNA and proteins were extracted and analyzed by quantitative PCR and pathscan enzyme-linked immunosorbent assays, respectively. RESULTS:In monocyte cells from human subjects with increased risk for diabetes and atherosclerosis, we found that gene expression, protein levels, and tyrosine phosphorylation of IRS2, but not InsR or IRS1, were decreased. TIMP3 was also reduced, along with insulin resistance, resulting in increased ectodomain shedding activity of the metalloprotease ADAM17. CONCLUSIONS:Systemic insulin resistance and subclinical atherosclerosis are associated with decreased IRS2 and TIMP3 expression in circulating monocytes.
journal_name
Diabetesjournal_title
Diabetesauthors
Cardellini M,Menghini R,Luzi A,Davato F,Cardolini I,D'Alfonso R,Gentileschi P,Rizza S,Marini MA,Porzio O,Lauro D,Sbraccia P,Lauro R,Federici Mdoi
10.2337/db11-0162subject
Has Abstractpub_date
2011-12-01 00:00:00pages
3265-70issue
12eissn
0012-1797issn
1939-327Xpii
db11-0162journal_volume
60pub_type
杂志文章相关文献
DIABETES文献大全abstract::A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.2337/diabetes.53.12.3193
更新日期:2004-12-01 00:00:00
abstract::Spirometry was performed on 88 children with insulin-dependent diabetes mellitus (IDDM) and 216 healthy controls living in Sheffield. Children with IDDM had significantly lower percentage predicted forced vital capacity (FVC) than did control children or reference norms. There was no evidence that the reduced FVC was ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.3.324
更新日期:1987-03-01 00:00:00
abstract::Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the ro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0134
更新日期:2012-06-01 00:00:00
abstract::Precise timing of the teratogenic period in diabetic pregnancy is of clinical importance since correction of the glucose intolerance during this period may protect the offspring from malformations. An experimental approach to elucidate this problem with regard to skeletal development was made in groups of pregnant str...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.12.1141
更新日期:1983-12-01 00:00:00
abstract::The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.10.3032
更新日期:2005-10-01 00:00:00
abstract::Estrogen-related receptor γ (ERRγ) is a major positive regulator of hepatic gluconeogenesis. Its transcriptional activity is suppressed by phosphorylation signaled by insulin in the fed state, but whether posttranslational modification alters its gluconeogenic activity in the fasted state is not known. Metabolically a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1523
更新日期:2016-10-01 00:00:00
abstract::The ATP-sensitive K(+) channel (K(ATP) channel) in pancreatic beta-cells is a critical regulator in insulin secretion. We previously reported that transgenic mice expressing a dominant-negative form (Kir6.2G132S) of Kir6.2, a subunit of the K(ATP) channel, specifically in beta-cells develop severe hyperglycemia in adu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-1459
更新日期:2006-07-01 00:00:00
abstract::Many individuals with diabetes experience impaired cardiac contractility that cannot be explained by hypertension and atherosclerosis. This cardiomyopathy may be due to either organ-based damage, such as fibrosis, or to direct damage to cardiomyocytes. Reactive oxygen species (ROS) have been proposed to contribute to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.3.777
更新日期:2003-03-01 00:00:00
abstract::Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo sub...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.6.762
更新日期:1996-06-01 00:00:00
abstract::Regulated exocytosis forms the basis for many intercellular signaling processes, for example, in hormone secretion or neurotransmitter release. During regulated exocytosis, the membrane of a secretory vesicle fuses with the plasma membrane in a tightly controlled reaction that is most often triggered by calcium. Recen...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.51.2007.s3
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVE:Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, re...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0724
更新日期:2008-07-01 00:00:00
abstract::The use of HIV protease inhibitors (PIs) has been associated with several metabolic changes, including lipodystrophy, hyperlipidemia, and insulin resistance. The etiology of these adverse effects remains unknown. PIs have recently been found to cause acute and reversible inhibition of GLUT4 activity in vitro. To deter...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.937
更新日期:2002-04-01 00:00:00
abstract::Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 20...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1557
更新日期:2003-06-01 00:00:00
abstract::Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restrict...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.6.1326
更新日期:2003-06-01 00:00:00
abstract::Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and ...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db12-0166
更新日期:2012-10-01 00:00:00
abstract::Adiponectin is an abundant adipose tissue-derived protein with important metabolic effects. Plasma adiponectin levels are decreased in obese individuals, and low adiponectin levels predict insulin resistance and type 2 diabetes. Two variants in the adiponectin gene ACDC have been previously associated with plasma adip...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.1.284
更新日期:2005-01-01 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::Type 1 diabetes presents clinically with overt hyperglycemia resulting from progressive immune-mediated destruction of pancreatic β-cells and associated metabolic dysfunction. Combined genetic and immunological studies now highlight deficiencies in both the interleukin-2 (IL-2) receptor and its downstream signaling pa...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db11-1213
更新日期:2012-01-01 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:OBJECTIVE:Common variants in the gene TCF7L2 confer the largest effect on the risk of type 2 diabetes. The present study was undertaken to increase our understanding of the mechanisms by which this gene affects type 2 diabetes risk. RESEARCH DESIGN AND METHODS:Eight subjects with risk-conferring TCF7L2 genotypes (TT o...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1169
更新日期:2010-02-01 00:00:00
abstract::Current evidence suggests that reactive oxygen species (ROS) may participate in the destruction of pancreatic beta-cells leading to type 1 diabetes. Genetic factors pre-disposing individual susceptibility to type 1 diabetes might therefore include those affecting the efficacy of ROS metabolism. In a direct in vivo tes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.46.10.1563
更新日期:1997-10-01 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::Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arte...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.448
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:Haptoglobin (Hp) is upregulated in both inflammation and obesity. The low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM) infiltration found in obesity, and low adiponectin have been implicated in the development of insulin resistance and hepatosteatosis. The aim of this work was...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1536
更新日期:2011-10-01 00:00:00
abstract::Diabetes is associated with a loss of somatosensory and motor function, leading to impairments in gait, balance, and manual dexterity. Data-driven neuroimaging studies frequently report a negative impact of diabetes on sensorimotor regions in the brain; however, relationships with sensorimotor behavior are rarely cons...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db19-0321
更新日期:2020-01-01 00:00:00
abstract::The success of the Edmonton Protocol for islet transplantation has provided new hope in the treatment of type 1 diabetes. This study reports on the assessment of 83 human islet grafts transplanted using the Edmonton Protocol since 1999. Cellular composition, as assessed by immunohistochemistry, showed a lower islet pu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.12.3107
更新日期:2004-12-01 00:00:00
abstract::In early 1988, a colony of GK rats was started in Paris with progenitors issued from F35 of the original colony reported by Goto and Kakisaki. When studied longitudinally up to 8 mo, GK rats showed as early as 1 mo (weaning) significantly higher basal plasma glucose (9 mM) and insulin levels (doubled), altered glucose...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.4.486
更新日期:1991-04-01 00:00:00
abstract::Glucagonlike peptide I (7-37) [GLP-I-(7-37)], encoded with glucagon and glucagonlike peptide II and intervening peptide II in the rat and human glucagon gene, is processed from proglucagon in both pancreas and intestine and is a potent stimulator of insulin secretion. Unequivocal insulin release from the isolated perf...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.3.338
更新日期:1989-03-01 00:00:00
abstract::Somatostatin-like immunoreactivity (SLI) concentrations were determined in human peripheral plasma using affinity chromatography followed by radioimmunoassay. In normal subjects, fasting SLI ranged from 2.9 to 22.0 pg/ml with a mean +/- SE value of 10.2 +/- 2.1 pg/ml. In totally pancreatectomized or gastrectomized pat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.6.471
更新日期:1981-06-01 00:00:00
abstract::This study addressed the controversial question of whether a negative-insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.36.8.959
更新日期:1987-08-01 00:00:00