Abstract:
:Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance.
journal_name
Diabetesjournal_title
Diabetesauthors
Prasai MJ,Mughal RS,Wheatcroft SB,Kearney MT,Grant PJ,Scott EMdoi
10.2337/db11-1740subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1981-9issue
6eissn
0012-1797issn
1939-327Xpii
db11-1740journal_volume
62pub_type
杂志文章相关文献
DIABETES文献大全abstract::The effects of glucose and diabetes on the high-affinity lofentanil-displaceable opiate-receptor binding in mouse brain membranes were studied to determine if the attenuation of opiate actions by hyperglycemia previously observed in our laboratory was due to a modification of receptor affinity or number. With membrane...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.10.1173
更新日期:1987-10-01 00:00:00
abstract::Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising ini...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1212
更新日期:2015-04-01 00:00:00
abstract::To investigate the early events in insulin signal transmission in liver, isolated rat hepatocytes were labeled with 32P, and proteins phosphorylated in response to insulin were detected by immunoprecipitation with anti-phosphotyrosine and anti-receptor antibodies and analyzed by sodium dodecyl sulfate (SDS)-polyacryla...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.1.66
更新日期:1991-01-01 00:00:00
abstract::Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. W...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.4.901
更新日期:2001-04-01 00:00:00
abstract::Diabetic hypoglycemia produces cognitive-motor slowing, which is assumed to increase risk of automobile crashes. This study investigated driving decrements during and after hypoglycemia, and the patients' awareness of driving decrements. We used a randomized, single-blind, crossover design and conducted the study at t...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diab.42.2.239
更新日期:1993-02-01 00:00:00
abstract::The aim of this study was to compare the effects of insulin and the insulinomimetic agent, englitazone, on functional end points and putative mediators of insulin action in 3T3-L1 adipocytes. Cells were incubated with englitazone for 48 h or with insulin for 10 or 30 min, or both, and 2-deoxy-D-[3H]glucose (2DG) uptak...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.2.179
更新日期:1998-02-01 00:00:00
abstract::To explore metabolic changes associated with the sorbitol accumulation and myo-inositol depletion observed in glomeruli of rats with experimental diabetes, we examined total and ouabain-inhibited adenosine triphosphatase (ATPase) activity in glomeruli isolated from control and streptozocin (STZ)-diabetic rats. Glomeru...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.11.1071
更新日期:1985-11-01 00:00:00
abstract::Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.5.466
更新日期:1983-05-01 00:00:00
abstract::Diabetes is characterized by altered metabolism of key molecules and regulatory pathways. The phenotypic expression of diabetes and associated complications encompasses complex interactions between genetic, environmental, and tissue-specific factors that require an integrated understanding of perturbations in the netw...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db14-0509
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVE:Vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. We have recently shown that vaspin mRNA expression in adipose tissue is related to parameters of obesity and glucose metabolism. However, the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1045
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1541
更新日期:2010-04-01 00:00:00
abstract::It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previou...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.39.2.217
更新日期:1990-02-01 00:00:00
abstract::Insulin-dependent diabetes mellitus (IDDM) is characterized by a metabolic and hormonal disarray that may be more evident during exercise. However, the metabolic response to exercise of different intensities has not been evaluated in IDDM. We therefore used stable isotope techniques and indirect calorimetry to quantif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.9.1066
更新日期:1995-09-01 00:00:00
abstract::Sterol regulatory element-binding protein (SREBP)-1 transcription factors play a central role in energy homeostasis by promoting glycolysis, lipogenesis, and adipogenesis. The sterol regulatory element-binding protein gene (SREBF)-1 is a good candidate gene for obesity and obesity-related metabolic traits such as type...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.8.2153
更新日期:2004-08-01 00:00:00
abstract::Hyperglycemia-induced alterations in mesangial (MES) cell function and extracellular matrix protein accumulation are seen in diabetic glomerulopathy. Recent studies have demonstrated that some of the effects of high glucose (HG) on cellular metabolism are mediated by the hexosamine biosynthesis pathway (HBP), in which...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.10.2355
更新日期:2001-10-01 00:00:00
abstract::Mutations in several genes cause nonautoimmune diabetes, but numerous patients still have unclear genetic defects, hampering our understanding of the development of the disease and preventing pathogenesis-oriented treatment. We used whole-genome sequencing with linkage analysis to study a consanguineous family with ea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1784
更新日期:2014-10-01 00:00:00
abstract::Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ bet...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.9.836
更新日期:1985-09-01 00:00:00
abstract::With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studie...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.7.1209
更新日期:2000-07-01 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:OBJECTIVE:To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects. RESEARCH DESIGN AND METHODS:Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzy...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1528
更新日期:2009-09-01 00:00:00
abstract::Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies...
journal_title:Diabetes
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2337/db11-1445
更新日期:2012-09-01 00:00:00
abstract::Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed interv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1390
更新日期:2016-04-01 00:00:00
abstract::We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. MC3-R and MC4-R were measured by quantitative autoradiography in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.2.267
更新日期:1999-02-01 00:00:00
abstract::The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the Ins2+/Akita mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1306
更新日期:2018-08-01 00:00:00
abstract::Human CD5+ B lymphocytes produce autoantibodies that bind to self- and exogenous antigens. Extremely high percentages of CD5+ B lymphocytes are present in the fetal and newborn periods, whereas they constitute only a minority of B lymphocytes in healthy adults. Increased percentages of circulating CD5+ lymphocytes hav...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.10.1314
更新日期:1991-10-01 00:00:00
abstract::A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are use...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.3.169
更新日期:1980-03-01 00:00:00
abstract::Increased pancreas mass and glucagon-positive adenomas have been suggested to be a risk associated with sitagliptin or exenatide therapy in humans. Novo Nordisk has conducted extensive toxicology studies, including data on pancreas weight and histology, in Cynomolgus monkeys dosed with two different human glucagon-lik...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1087
更新日期:2014-07-01 00:00:00
abstract::Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.2.474
更新日期:2004-02-01 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::Type 2 diabetes (T2D) is hallmarked by insulin resistance, impaired insulin secretion, and increased hepatic glucose production. The worldwide increasing prevalence of T2D calls for efforts to understand its pathogenesis in order to improve disease prevention and management. Recent genome-wide association studies have...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1921
更新日期:2014-10-01 00:00:00