Abstract:
:Diabetic hearts exhibit decreased responsiveness to stimulation by beta-adrenoreceptor (beta-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of beta-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to beta1-AR agonist stimulation, but not to beta2-AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac beta1-, beta2-, and beta3-ARs and looked at whether these changes could be restored with insulin treatment. Using reverse transcription-polymerase chain reaction (RT-PCR), PAGE, and Western blot analysis, we found that beta1-AR mRNA and protein levels decreased by 34.9 +/- 5.8 and 44.4 +/- 5.8%, respectively, in 14 week-STZ-treated diabetic rat hearts when compared with age-matched controls. On the other hand, mRNA levels encoding beta2- and beta3-ARs increased by 72.5 +/- 16.6 and 97.3 +/- 26.1%, respectively. Although the latter translated into a proportional increase in beta3-AR protein levels (100.0 +/- 17.0%), beta2-AR protein levels decreased to 82.6 +/- 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored beta1-AR mRNA and protein levels to 60.1 +/- 8.4 and 83.2 +/- 5.0%, respectively, of control. Although insulin treatment minimally attenuated the rise in mRNA levels encoding beta2- and beta3-ARs, the steady-state levels of these proteins returned to near control values. These data suggest that the decreased responsiveness of diabetic hearts to stimulation of beta-AR agonists may be due to a decrease in beta1-AR and an increase beta3-AR expression.
journal_name
Diabetesjournal_title
Diabetesauthors
Dinçer UD,Bidasee KR,Güner S,Tay A,Ozçelikay AT,Altan VMdoi
10.2337/diabetes.50.2.455subject
Has Abstractpub_date
2001-02-01 00:00:00pages
455-61issue
2eissn
0012-1797issn
1939-327Xjournal_volume
50pub_type
杂志文章相关文献
DIABETES文献大全abstract::Activation of the receptor for advanced glycation end products (RAGE) reportedly triggers a variety of proinflammatory responses. However, our previous work revealed that RAGE-binding AGEs free of endotoxin were incapable of inducing vascular cell adhesion molecule-1 (VCAM-1) or tumor necrosis factor-alpha (TNF-alpha)...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.3.743
更新日期:2004-03-01 00:00:00
abstract::The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical dia...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1115
更新日期:2016-03-01 00:00:00
abstract::Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0828
更新日期:2020-02-01 00:00:00
abstract::This study investigated changes in levels of mRNAs encoding the three neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal root ganglia of control and streptozocin-induced diabetic rats. After 8 weeks of diabetes...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.1.25
更新日期:1995-01-01 00:00:00
abstract::Repeated large-volume blood withdrawals started at a young age previously appeared to correct lymphopenia and prevent diabetes in Ottawa diabetes-prone BB (BBdp) rats. Therefore, we sought an early effect 24 h after withdrawal of 25% of estimated blood volume and then reexamined the long-term effects in BBdp rats. The...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.9.1099
更新日期:1990-09-01 00:00:00
abstract::Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endoto...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1491
更新日期:2007-07-01 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
abstract::Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). W...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db10-0902
更新日期:2012-02-01 00:00:00
abstract::Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi16-0069
更新日期:2017-07-01 00:00:00
abstract::Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-contai...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.4.509
更新日期:1993-04-01 00:00:00
abstract::Recent large-scale epidemiological studies demonstrate that blood concentrations of immunoreactive insulin predict the development of NIDDM and IDDM and are associated with the risk of several degenerative diseases, such as coronary and peripheral vessel atherosclerosis, hypertension, and dyslipidemia. The reliability...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.2.242
更新日期:1996-02-01 00:00:00
abstract::Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor known as a key molecule in the development and functions of the beta-cells. In a previously performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-0620
更新日期:2006-05-01 00:00:00
abstract::Proinsulin folding within the endoplasmic reticulum (ER) remains incompletely understood, but it is clear that in mutant INS gene-induced diabetes of youth (MIDY), progression of the (three) native disulfide bonds of proinsulin becomes derailed, causing insulin deficiency, β-cell ER stress, and onset of diabetes. Here...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1345
更新日期:2016-04-01 00:00:00
abstract::Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.7.842
更新日期:1987-07-01 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::Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1737
更新日期:2002-06-01 00:00:00
abstract::Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.3.284
更新日期:1987-03-01 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat type 2 diabetes, and transient GLP-1 administration improved cardiac function in humans after acute myocardial infarction (MI) and percutaneous revascularization. However, the consequences of GLP-1R activation before ischemic myocardial inju...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1193
更新日期:2009-04-01 00:00:00
abstract::Glucagon-like peptide 1 receptor (GLP-1R) imaging with radiolabeled exendin has proven to be a powerful tool to quantify β-cell mass (BCM) in vivo. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose (BG) levels on GLP-1R-mediated exendin uptake in both murine ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0616
更新日期:2020-11-01 00:00:00
abstract::Apoptosis is a physiological form of cell death that occurs during normal development, and critical mediators of this process include caspases, reactive oxygen species, and Ca2+. Excessive apoptosis of the pancreatic beta-cell has been associated with diabetes. Consequently, apoptosis research has focused on how infil...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2007.s44
更新日期:2001-02-01 00:00:00
abstract::In patients with diabetes, altered diurnal blood pressure (BP) regulation (high night-to-day [N/D] ratio, or "nondipping") is associated with increases in albumin excretion and a decline in the glomerular filtration rate (GFR) by an unknown mechanism. Because it is known that renin angiotensin system (RAS) activation ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.7.1806
更新日期:2003-07-01 00:00:00
abstract::Increased glomerular filtration rate and kidney size early in the course of experimental and human diabetes may be important in the pathogenesis of diabetic nephropathy. Factors causing these renal functional changes are unknown. The isolated, perfused rat kidney (IPRK) was used to study the effects of elevated glucos...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.4.360
更新日期:1985-04-01 00:00:00
abstract::Duct-occluded segmental-pancreas transplants develop progressive fibrotic atrophy, even though endocrine function seems to be unaffected. To determine end-stage size of the graft and to evaluate magnetic resonance imaging (MRI) and computed tomography (CT), these imaging techniques were applied in eight patients with ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.1.s24
更新日期:1989-01-01 00:00:00
abstract::Large glucagon immunoreactive substances, extracted from the fetal bovine pancreas and separated by gel filtration in the presence of 6 M guanidinium-hydrochloride, were submitted to lectin-sepharose affinity column chromatograph. Gel-filtered peak I (approximately 45 K delta) and peak II (approximately 10 K delta) in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diacare.31.11.1002
更新日期:1982-11-01 00:00:00
abstract::Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality-iatrogenic hyperinsulinemia-principally drives ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/dbi19-0026
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:Reactive oxygen species (ROS) is one of most important factors in impaired metabolism secretion coupling in pancreatic β-cells. We recently reported that elevated ROS production and impaired ATP production at high glucose in diabetic Goto-Kakizaki (GK) rat islets are effectively ameliorated by Src inhibition,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0021
更新日期:2011-01-01 00:00:00
abstract::Pancreatic beta-cells are more sensitive to several toxins (e.g., streptozotocin, alloxan, cytokines) than the other three endocrine cell types in the islets of Langerhans. Cytokine-induced free radicals in beta-cells may be involved in beta-cell-specific destruction in type 1 diabetes. To investigate if this sensitiv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.12.2324
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. RESEARCH DESIGN AND METHODS:We generated a new transgenic model allowing near-total α-cell removal specifically in...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0876
更新日期:2011-11-01 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:OBJECTIVE:Pregnancy induces a state of immunological tolerance that aims at suppressing immune responses against the fetus and has been linked to temporal remission of preexisting autoimmune disorders. To understand the mechanisms of this reversible immune regulation, we investigated the role of a key pregnancy hormone...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1727
更新日期:2007-06-01 00:00:00