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 would be present in long-term ATOCs but could be rendered nondiabetogenic by co-culture with appropriate antigens. We observed that cells recovered from adult diabetes-resistant BB (BBDR) rat thymi cultured for up to 14 days can adoptively transfer disease to athymic WAG-rnu/rnu rats treated with polyinosinic: polycytidylic acid and a monoclonal antibody to preclude development of ART2a+ regulatory T-cells. Co-culture of adult BBDR thymi in the presence of BBDR thyrocytes had no effect on the ability of recovered cells to induce diabetes in 70-80% of adoptive recipients. In contrast, co-culture in the presence of islets prevented transfer of diabetes, on average, in >90% of recipients. Fresh islets, frozen islets, and islets pretreated with streptozotocin to deplete insulin were equally effective in preventing diabetes, but none prevented insulitis in nondiabetic recipients. Co-culture in the presence of islets was not associated with detectable alterations in phenotype or in the secretion of gamma-interferon or interleukin-4, either in cultures or in cells recovered from adoptive recipients. We conclude that islet antigens involved in the initiation of autoimmune diabetes in BB rats may be absent or deficient in BB rat thymi. Exposure of ATOCs to exogenous islets may lead to deletion or anergy of diabetogenic T-cells or to the positive selection of regulatory T-cells.
journal_name
Diabetesjournal_title
Diabetesauthors
Whalen BJ,Marounek J,Weiser P,Appel MC,Greiner DL,Mordes JP,Rossini AAdoi
10.2337/diabetes.50.5.972subject
Has Abstractpub_date
2001-05-01 00:00:00pages
972-9issue
5eissn
0012-1797issn
1939-327Xjournal_volume
50pub_type
杂志文章相关文献
DIABETES文献大全abstract::Insulin resistance and type 2 diabetes are associated with elevated circulating levels of insulin, nonesterified fatty acids (NEFAs), and lipoprotein remnants. Extracellular matrix proteoglycan (PG) alterations are also common in macro- and microvascular complications of type 2 diabetes. In liver, extracellular hepara...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.9.2126
更新日期:2001-09-01 00:00:00
abstract::It has been hypothesized that type 1 diabetes is initiated by neonatal physiological pancreatic beta-cell death, indicating that the early stages of this autoimmune response may reflect a dysregulated response to immune "danger" signals. One potential danger signal is ATP, high concentrations of which stimulate the pu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.8.2012
更新日期:2004-08-01 00:00:00
abstract::Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been implicated in the control of blood glucose by its potent effect on expression and signaling of various nuclear receptors. To understand the role of COUP-TFII in glucose homeostasis, conditional COUP-TFII-deficient mice were generated and ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1357
更新日期:2005-05-01 00:00:00
abstract:OBJECTIVE:We sought to examine the molecular mechanisms underlying permanenent neonatal diabetes mellitus (PNDM) in a patient with a heterozygous de novo L225P mutation in the L0 region of the sulfonylurea receptor (SUR)1, the regulatory subunit of the pancreatic ATP-sensitive K(+) channel (K(ATP) channel). RESEARCH D...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1746
更新日期:2007-05-01 00:00:00
abstract::Elevation of glucagon levels and increase in α-cell mass are associated with states of hyperglycemia in diabetes. Our previous studies have highlighted the role of nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls glucagon secretion and α-cell mass. In the current studies we investigated the effe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0440
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVE:The Vhlh gene codes for the von Hippel-Lindau protein (VHL), a tumor suppressor that is a key player in the cellular response to oxygen sensing. In humans, a germline mutation in the VHL gene leads to the von Hippel-Lindau disease, a familial syndrome characterized by benign and malignant tumors of the kidney...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-0749
更新日期:2009-02-01 00:00:00
abstract::The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.5.602
更新日期:1990-05-01 00:00:00
abstract::Metformin is the most widely prescribed medication for the treatment of type 2 diabetes (T2D). However, gastrointestinal (GI) side effects develop in ~25% of patients treated with metformin, leading to the discontinuation of therapy in ~5% of cases. We hypothesized that reduced transport of metformin via organic catio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1388
更新日期:2015-05-01 00:00:00
abstract::Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin s...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.54.2.340
更新日期:2005-02-01 00:00:00
abstract::Successful islet transplantation depends on the infusion of sufficiently large quantities of islets, but only a fraction of transplanted islets can survive and become engrafted, and yet the underlying mechanism remains unclear. In this study, we examined the effect of sirolimus, a key component of the immunosuppressiv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0173
更新日期:2006-09-01 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::Variation in the calpain 10 gene has recently been shown to be associated with type 2 diabetes by positional cloning. Since then, studies on calpain 10 have been started in correlation with diabetes and insulin-mediated signaling. In this review, the activation mechanism of calpain by calcium ions, which is essential ...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.53.2007.s12
更新日期:2004-02-01 00:00:00
abstract::The epidemic of obesity and type 2 diabetes has increased interest in pathways that affect energy balance in mammalian systems. Brown fat, in all of its dimensions, can increase energy expenditure through the dissipation of chemical energy in the form of heat, using mitochondrial uncoupling and perhaps other pathways....
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db15-0318
更新日期:2015-07-01 00:00:00
abstract::The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a cl...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0287
更新日期:2019-10-01 00:00:00
abstract::Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inv...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.4.339
更新日期:1982-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS:Characterization of clinical and biochemical parameters and β-cell function of 411 Medalists with correlation wi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0676
更新日期:2010-11-01 00:00:00
abstract::Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture med...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.9.850
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0839
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVE:Evaluate if Erb B2 activation and the loss of caveolin-1 (Cav1) contribute to the pathophysiological progression of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS:Cav1 knockout and wild-type C57BL/6 mice were rendered diabetic with streptozotocin, and changes in motor nerve conduction velo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0594
更新日期:2009-11-01 00:00:00
abstract::Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.9.2389
更新日期:2003-09-01 00:00:00
abstract::The present study was performed to assess the potential relationship between the low T3 syndrome and hypothyroidism. Comparative studies were performed on the relative effects of diabetes and insulin on heparin-releasable adipose lipoprotein lipase (LPL) in the intact and hypothyroid rat. Hypothyroidism for 10 days (T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.12.1266
更新日期:1985-12-01 00:00:00
abstract::Vascular complications are the leading causes of morbidity and mortality in diabetic patients. The contribution of platelets to thromboembolic complications is well documented, but their involvement in the initiation of the atherosclerotic process is of rising interest. Thus, the aim of the present study was to evalua...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.4.1046
更新日期:2004-04-01 00:00:00
abstract::One hundred fifty-four selected patients with nonketotic diabetes diagnosed between the ages of 35 and 75 yr and treated with diet or oral hypoglycemic agents for at least 1 yr were investigated for parameters of glycemic control (weight loss, blood glucose, and glycosylated hemoglobin), islet cell function (fasting a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.35.2.237
更新日期:1986-02-01 00:00:00
abstract:OBJECTIVE:Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0287
更新日期:2010-07-01 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::The effect of 4 wk of streptozocin (STZ)-induced diabetes on the transmission time of the auditory-evoked brain stem response (ABR) was examined in conscious male Sprague-Dawley rats. Distal nerve transmission time of the auditory pathway (latency of peak II), which includes conduction along the 8th cranial nerve, inc...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.4.500
更新日期:1987-04-01 00:00:00
abstract::Net hepatic glucose uptake (NHGU) is an important contributor to postprandial glycemic control. We hypothesized that NHGU is reduced during normal pregnancy and in a pregnant diet-induced model of impaired glucose intolerance/gestational diabetes mellitus (IGT/GDM). Dogs (n = 7 per group) that were nonpregnant (N), no...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0875
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes. RESEARCH DESIGN AND METHO...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0263
更新日期:2011-11-01 00:00:00
abstract::The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of 111In-diethylenetriaminepentaacetic acid-exendin-3 (111In-exendin) in a rat model that closely mimics the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1312
更新日期:2018-10-01 00:00:00
abstract::The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.40.8.952
更新日期:1991-08-01 00:00:00