Abstract:
:Activation of self-reactive T cells that specifically destroy the pancreatic beta-cells is one of the hallmarks in the development of type 1 diabetes. Thus, for prevention and treatment of this autoimmune disease, approaches to induce and maintain T cell tolerance toward the beta-cells, especially in islet transplantation, have been actively pursued. Noticeably, many of the recent protocols for inducing transplant tolerance involve blockade of positive T cell costimulation extrinsically. Though highly effective in prolonging graft survival, these strategies alone might not be universally sufficient to achieve true tolerance. As the mystery of the suppressive and regulatory T cells unfolds, it is becoming appreciated that exploiting the intrinsic molecular and cellular mechanisms that turn off an immune response would perhaps facilitate the current protocols in establishing T cell tolerance. In this perspective, here we summarize the recent findings on the negative costimulation pathways, in particular, the newly identified PD-1 : PD-L interactions. On the basis of these observations, we propose a new principle of curtailing pathogenic T cell response in which blockade of positive T cell costimulation is reinforced by concurrent engagement of the negative costimulation machinery. Such a strategy may hold greater hope for therapeutic intervention of transplant rejection and autoimmune diseases.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Gao W,Demirci G,Li XCdoi
10.1002/dmrr.345keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
179-85issue
3eissn
1520-7552issn
1520-7560journal_volume
19pub_type
杂志文章,评审abstract:BACKGROUND:Latent autoimmune diabetes in adults (LADA) exhibits significant clinical heterogeneity, but the underlying causes remain unclear. The aim of this study was to investigate whether age of onset of LADA contributes to the observed clinical heterogeneity by comparing the clinical, metabolic, and immunogenetic c...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3068
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate saccharide chains. The enzyme promotes cell adhesion, migration and invasion, and was shown to play a significant role in cancer metastasis and angiogenesis. METHODS:The present study focuses on the involvement of heparanase in autoimmu...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.868
更新日期:2008-07-01 00:00:00
abstract::Hypoglycaemia is inevitable when striving for low HbA1c values. Nocturnal hypoglycaemia often occurs without symptoms, but results in diminished next day well-being and hypoglycaemia unawareness. Frequency of nocturnal hypoglycaemia was first assessed in research ward settings, but suffered from insufficient glucose s...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.513
更新日期:2004-11-01 00:00:00
abstract::The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. In conjunction with advice from internal and external reviewers and expert consultants in the field, this update is based on a systematic review of ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.3283
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose retu...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.951
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been suggested to be a part of the insulin resistance syndrome, and recent data suggest that adipose tissue participates in the production of PAI-1. We examined the expression and insulin regulation of subcutaneous adipose tissue PAI-1 ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/1520-7560(2000)9999:9999<::aid-dmrr148>3.0
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:Mutating the insulin B:9-23 peptide prevents diabetes in NOD mice. Thus, the trimolecular complex of I-Ag7-insulin B:9-23 peptide-TCR may be essential for the development of spontaneous diabetes. Pathogenic T cells recognize the B:9-23 peptide presented by I-Ag7 in what is termed register 3, with the B22 bas...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.1252
更新日期:2011-11-01 00:00:00
abstract::Neuropathy is a frequent complication in diabetes and most commonly seen as distal symmetrical sensorimotor polyneuropathy (PN). Involvement of the motor system is infrequently seen at the clinical examination. However, with the application of quantitative techniques, that is, isokinetic dynamometry, type 1 and type 2...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.2257
更新日期:2012-02-01 00:00:00
abstract::Studies on skeletal involvement in patients with diabetes mellitus have generated conflicting results, largely because of the pathogenetic complexity of the condition. Several mechanisms may contribute to skeletal damage, including the increased urinary excretion coupled with the lower intestinal absorption of calcium...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.449
更新日期:2004-05-01 00:00:00
abstract::The actual pathophysiology behind gestational diabetes mellitus (GDM) is still unclear, but a deterioration in insulin resistance beyond that induced by pregnancy, combined with beta cell dysfunction, plays a key role. Interventions that help improve glucose tolerance by attenuating pregnancy-induced insulin resistanc...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.2402
更新日期:2013-07-01 00:00:00
abstract::Prevention of diabetic foot ulcers is important to reduce the burden of diabetic foot disease. However, we found that ulcer prevention is underexposed in research and clinical practice. Barriers to explain this are seen in patient's goal-setting; in the lack of interdisciplinary teams for ulcer prevention; in sample s...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3234
更新日期:2020-03-01 00:00:00
abstract::In Mediterranean countries, the incidence (per 100,000 per year) of Type 1 diabetes in children aged under 15 years shows wide variation from country to country, ranging from 2.45 in Macedonia to 34.4 in Sardinia. By interacting with environmental factors such as diet, toxins or viral infections, the HLA plus non-HLA ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/(sici)1520-7560(199903/04)15:2<133::aid-dm
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:The aim of this study was to assess the clinical implications of calculating an individualized HbA1c target using a recently published algorithm in a real-life clinical setting. METHODS:General practitioners (GPs) from the Spanish Society of Family Medicine Diabetes Expert Group were invited to participate ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2976
更新日期:2018-03-01 00:00:00
abstract::A recent study from Gallagher et al. aimed to investigate the effect of a new depeptidyl-peptidase-4 inhibitor, MK-0626, on bone turnover in a mouse model developing insulin resistance and diabetes (MKR mice). Authors have found that treatment with MK-0626 did not affect either MKR mice fasting glucose or parameters o...
journal_title:Diabetes/metabolism research and reviews
pub_type: 评论,杂志文章
doi:10.1002/dmrr.2505
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Women with obesity and type 2 diabetes (T2D) are at greater risk of dying from breast cancer than women without these conditions. Obesity and T2D are associated with insulin resistance and endogenous hyperinsulinemia and are more common in Black women. There is increasing disparity in breast cancer mortality...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2795
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Type 2 diabetes is a risk factor for stroke and confers increased risk of poor outcome and further vascular events following stroke. Hyperuricaemia occurs commonly in patients with type 2 diabetes, but its significance as a predictor of outcome following stroke is uncertain. We sought to investigate the prog...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.585
更新日期:2006-01-01 00:00:00
abstract::Now that the reduction in beta-mass has been clearly established in humans with type 2 diabetes mellitus (T2DM) 1-4, the debate focuses on the possible mechanisms responsible for decreased beta-cell number and impaired beta-cell function and their multifactorial etiology. Appropriate inbred rodent models are essential...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.566
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:A nested case-control (NCC) design within a prospective cohort study can realize substantial benefits for biomarker studies. In this context, it is natural to consider the sample availability in the selection of controls to minimize data loss when implementing the design. However, this violates the randomnes...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3204
更新日期:2020-01-01 00:00:00
abstract::Excess visceral fat can regulate insulin sensitivity and energy metabolism by releasing adipokines into the circulation which then bind with their cognate receptors in various tissues and alter glucose and lipid metabolism. Circulating levels of adiponectin, which promotes glucose uptake into skeletal muscle and incre...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.778
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Cross-sectional and family studies identified angiotensin-converting enzyme (ACE) gene as a risk factor for diabetic nephropathy (DN). The contribution of ACE gene variants to DN development and progression is controversial and varies among different ethnic/racial groups. METHODS:We investigated the associa...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.1006
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:To evaluate the association between fasting plasma glucose (FPG) and mortality by gender. METHODS:A total of 17 248 eligible participants from a rural Chinese prospective cohort population were included. The same questionnaire interview and anthropometric and laboratory measurements were performed at both b...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3129
更新日期:2019-05-01 00:00:00
abstract::Foot problems complicating diabetes are a source of major patient suffering and societal costs. Investing in evidence-based, internationally appropriate diabetic foot care guidance is likely among the most cost-effective forms of healthcare expenditure, provided it is goal-focused and properly implemented. The Interna...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.2694
更新日期:2016-01-01 00:00:00
abstract:AIMS:To assess the validity of the diagnostic codes relating to diabetic foot ulcer (DFU) in the electronic medical records of a large integrated care provider and to assess the prevalence of DFU among its members. MATERIALS AND METHODS:Data were obtained from the diabetes registry of Maccabi Healthcare Services (MHS)...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.3094
更新日期:2019-02-01 00:00:00
abstract::The prevalence of diabetes mellitus in primary hyperparathyroidism is approximately 8% and that of primary hyperparathyroidism in diabetic patients is approximately 1%. Both values are about three-fold higher than the respective expected prevalences in general populations. Patients with both disorders are over 40 year...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.199
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:There is a controversy about self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes who are not using insulin. Randomized trials are limited in duration, size, and validity. METHODS:Systematic search for randomized trials and observational studies published since 1990. For inclusion studie...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.749
更新日期:2007-09-01 00:00:00
abstract::Around one of three diabetic patients is affected by distal symmetric polyneuropathy (DSP) which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity and increased mortality. Treatment is based on four cornerstones: (1) multifactori...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.817
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Body mass index (BMI) is associated with death in a V-shaped manner in general populations but it is unknown whether BMI or other risk factors also exhibit V-shaped relationships with death in type 2 diabetic patients. METHODS:A prospective cohort of 7534 Chinese, type 2 diabetic patients enrolled since 199...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.792
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well-defined, only limited information is available on alpha cells. This study evaluates the long-term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation. METHODS:Cl...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.663
更新日期:2007-03-01 00:00:00
abstract::Diabetic foot disease is an important complication of diabetes. The development and outcome of foot ulcers are related to the interplay between numerous diabetes-related factors such as nerve dysfunction, impaired wound healing and microvascular and/or macrovascular disease.The formation of advanced glycation end prod...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章,评审
doi:10.1002/dmrr.861
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:Malonyl-CoA, an allosteric inhibitor of carnitine palmitoyl transferase, controls the oxidation of fatty acids in muscle and other tissues by regulating their entrance into mitochondria. The level of malonyl-CoA in muscle is influenced by the uptake of energy substrates such as glucose, the precursor of its ...
journal_title:Diabetes/metabolism research and reviews
pub_type: 杂志文章
doi:10.1002/dmrr.288
更新日期:2002-05-01 00:00:00