Abstract:
:Insulin exerts its biological effects through a plasma membrane receptor that possesses a tyrosine-kinase activity. This tyrosine-kinase activity depends on the autophosphorylation of the receptor on tyrosine residues and on its dephosphorylation by protein tyrosine-phosphatases. The discovery of pharmacological agents that specifically stimulate the autophosphorylation of the insulin receptor or inhibit its dephosphorylation will be of great importance for the treatment of insulin resistant or insulin deficient patients. Bioluminescence Resonance Energy Transfer (BRET) has developed in recent years as a new technique to study protein-protein interactions. In the BRET technique, one partner is fused to Renilla luciferase, whereas the other partner is fused to a fluorescent protein (e.g. YFP, Yellow Fluorescent Protein). The luciferase is excited by addition of its substrate, coelenterazine. If the two partners interact, resonance energy transfer occurs between the luciferase and the YFP, and a fluorescent signal, emitted by the YFP, can be detected. Our work indicates that this methodology could be an important tool for the search of molecules that activate insulin receptor autophosphorylation or that inhibit its dephosphorylation. Indeed, we first showed that the activation of the insulin receptor by different ligands can be monitored using a chimeric receptor with one B-subunit fused to Renilla luciferase and the other B-subunit fused to YFP. The conformational changes induced by different ligands could be detected as an energy transfer (BRET signal) between the luciferase and the YFP, that reflects the activation state of the receptor. This methodology allows for rapid analysis of the effects of agonists on insulin receptor activity and may therefore be used in high-throughput screening for the discovery of molecules with insulin-like properties. More recently, we demonstrated that the BRET methodology could also be used to monitor the interaction of the insulin receptor with protein tyrosine-phosphatase 1B, one of the main tyrosine-phosphatase that controls its activity. HEK cells were co-transfected with the insulin receptor fused to Renilla luciferase and a substrate-trapping mutant of PTP1B (PTP1B-D181A) fused to YFP. Insulin-induced BRET signal could be followed in real time for more than 30 min. Therefore, this methodology can also be used in high-throughput screening for the search of molecules that will specifically disrupt the interaction between the insulin receptor and PTP1B.
journal_name
Diabetes Metabjournal_title
Diabetes & metabolismauthors
Issad T,Boute N,Boubekeur S,Lacasa D,Pernet Kdoi
10.1016/s1262-3636(07)70016-2subject
Has Abstractpub_date
2003-04-01 00:00:00pages
111-7issue
2 Pt 1eissn
1262-3636issn
1878-1780pii
MDOI-DM-04-2003-29-2-1262-3636-101019-ART2journal_volume
29pub_type
杂志文章,评审abstract:AIM:Recent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA1c target and the occurrence of major clinical events under...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,多中心研究
doi:10.1016/j.diabet.2016.05.008
更新日期:2017-02-01 00:00:00
abstract:AIM:The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D). METHODS:In this cross-s...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2011.05.005
更新日期:2011-12-01 00:00:00
abstract::The CGMS (Continuous Glucose Monitoring System) is a portable device allowing continuous measuring of glucose. It provides recordings of at least 72 h, during which 288 measures/day are performed. Results are visualised in the form of a set of curves, illustrating the variations in blood glucose levels over time. The ...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:10.1016/s1262-3636(07)70258-6
更新日期:2006-04-01 00:00:00
abstract:AIM:There is growing evidence that periodontal disease may favour the incidence or aggravation of diabetes and its complications. To investigate the issue, we conducted a meta-analysis of the effect of periodontal therapy on glycaemic control in diabetic patients. METHODS:A literature search was carried out using seve...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,meta分析
doi:10.1016/j.diabet.2008.03.006
更新日期:2008-11-01 00:00:00
abstract:AIM:This study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease. METHODS:A total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2013.03.006
更新日期:2013-09-01 00:00:00
abstract::To determine the effect of benfluorex on glycaemic control in obese insulin-requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated after a 1-month run-in followed by a 3-month double-blind treatment period (3 tablets dai...
journal_title:Diabetes & metabolism
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1998-02-01 00:00:00
abstract:INTRODUCTION:Although it is important to screen women who have had gestational diabetes mellitus (GDM) for abnormal post-partum glucose levels, such testing is rarely performed. The aim of this study was to use data from the first observational phase of the IMPACT study to determine rates of screening within 6 months o...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,多中心研究
doi:10.1016/j.diabet.2013.12.002
更新日期:2014-04-01 00:00:00
abstract:AIMS:To report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canaglifl...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.diabet.2015.10.003
更新日期:2016-02-01 00:00:00
abstract::Diabetic retinopathy rarely occurs before puberty and is never proliferative in prepubescent children. On the opposite, puberty and adolescence are high-risk periods for diabetic retinopathy progression, and call for strict ophthalmologic monitoring. The period between 16 and 18 years of age is particularly critical. ...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2003-06-01 00:00:00
abstract::The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabol...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVES:To test the hypothesis that smokers have a higher frequency of the metabolic syndrome, and a syndrome with different characteristics than non-smokers. MATERIAL AND METHODS:The 2,569 men and 2,637 women included in the D.E.S.I.R. study, aged 30-64 years, volunteers from ten French Social Security Health Exam...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,多中心研究
doi:10.1016/s1262-3636(07)70031-9
更新日期:2003-06-01 00:00:00
abstract:AIMS:The objective of the present investigation was to study the production of IL-1, IL-6, IL-10, IFNgamma and TNFalpha in cultures of peripheral blood mononuclear cells (PBMC) taken from type 1 diabetic patients with inadequate metabolic control. METHODS:Seventeen type 1 diabetic patients and a gender- and age-matche...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2007.10.001
更新日期:2007-12-01 00:00:00
abstract::The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic tre...
journal_title:Diabetes & metabolism
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::To implement preventive policies of disability in older diabetic people, the role of diabetes in the disablement process should be investigated. Diabetes mellitus is consistently associated with a higher prevalence of disability at all states, as well as with a progression in disability states and may be considered as...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:10.1016/s1262-3636(07)80058-9
更新日期:2007-04-01 00:00:00
abstract::Preliminary results of an observational study are described in 50 unselected diabetic patients treated with insulin pens. The study was conducted to detect the presence of unexpected material in needles and cartridges after a single insulin injection. The injection was done by a trained nurse with the patient's usual ...
journal_title:Diabetes & metabolism
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract:AIM:To investigate the balance between parameters of oxidative stress and antioxidant defences in the mitochondria of peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients with late complications. METHODS:Ten type 2 diabetic patients with late diabetic complications and 10 age-matched healthy voluntee...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2007.10.011
更新日期:2008-04-01 00:00:00
abstract::ATP-sensitive potassium channels (K(ATP)) couple cell metabolism to electrical activity by regulating potassium movement across the membrane. These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:10.1016/S1262-3636(07)70311-7
更新日期:2006-12-01 00:00:00
abstract:AIM:The present study investigated the cyclooxygenase (COX) pathway to elucidate any changes that may be involved in the mechanism(s) underlying diabetic fetopathy. METHODS:Diabetes was induced in female rats (n=12) by two successive daily injections of 55 mg/kg streptozotocin, while control animals (n=10) were inject...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2009.06.009
更新日期:2010-02-01 00:00:00
abstract::Insulin-requiring diabetes (IRD) is a condition of permanent blood glucose imbalance which occurs despite a regulated diet and treatment with maximum doses of oral anti-diabetic drugs (glibenclamide 15 mg/d + metformin 1,700 mg/d). This report describes the results of a 2-year prospective study in 75 IRD patients trea...
journal_title:Diabetes & metabolism
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Prevalence of non-alcoholic steatohepatitis (NASH) rises steadily in Western countries with the obesity epidemic. NASH is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. The cannabinoid system is increasingly emerging as a crucial mediator of acute and chro...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/S1262-3636(08)74604-4
更新日期:2008-12-01 00:00:00
abstract::Glucagon-like peptide (GLP)-1 action involves both endocrine and neural pathways to control peripheral tissues. In diabetes the impairment of either pathway may define different subsets of patients: some may be better treated with GLP-1 receptor agonists that are more likely to directly stimulate beta-cells and extrap...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2013.02.005
更新日期:2013-04-01 00:00:00
abstract:AIM:To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D). METHODS:From 2009 to 2012, outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was measured ev...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2017.09.001
更新日期:2018-03-01 00:00:00
abstract:AIM:Cholesterol intake is associated with the risk for type 2 diabetes mellitus, but no previous studies have evaluated its role regarding the risk of gestational diabetes mellitus (GDM). We investigate the relation between cholesterol intake and GDM. METHODS:At screening for GDM, 335 pregnant women were evaluated for...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2006.07.002
更新日期:2007-02-01 00:00:00
abstract::Our society is currently facing an epidemic of diabetes and heart failure. Historically, certain cardiology treatments, mainly beta-blockers, have been considered 'dangerous' in diabetic patients, but the time has come for personalized medicine to be applied in the field of cardiology, especially in heart failure (HF)...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.diabet.2015.06.004
更新日期:2015-12-01 00:00:00
abstract::To determine whether insulin delivered into portal circulation by an implanted pump reversed abnormalities in lipoprotein composition in insulin-dependent diabetes mellitus, 10 well-controlled normolipidaemic patients were studied after conventional intensive sub-cutaneous (ISC) insulin management and then 3 and 6 mon...
journal_title:Diabetes & metabolism
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE:To assess the effectiveness of a patient education program on diabetes control. METHODS:A pre-test post-test pre experimental study was performed with 87 insulin treated diabetic patients followed in the chronic disease unit of Kelibia district (Nabeul, Tunisia). Subjects received education in 6 monthly sess...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/s1262-3636(07)70207-0
更新日期:2005-09-01 00:00:00
abstract::Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:10.1016/s1262-3636(03)72787-6
更新日期:2003-09-01 00:00:00
abstract::In Type 1 diabetes, high circulating growth hormone (GH) in conjunction with low plasma insulin-like growth factor-I (IGF-I) is indicative of a hepatic GH-resistance profile since the liver is the main source of circulating IGF-I. The reduction in specific growth hormone binding protein (GHBP), corresponding to the ex...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:
更新日期:1996-07-01 00:00:00
abstract:AIM:Cardiovascular autonomic neuropathy (CAN) is a common but often overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early on in patients with diabetes. In this study, SUDOSCAN, a new non-invasive device that assesses sudomotor function was compared to methods generally...
journal_title:Diabetes & metabolism
pub_type: 杂志文章
doi:10.1016/j.diabet.2012.09.004
更新日期:2013-04-01 00:00:00
abstract::Bariatric surgery can be proposed to address severe obesity associated with comorbid conditions, when medical treatment has failed. Three surgical techniques are currently available, including 2 using coelioscopy. Short term results are encouraging regarding weight loss, which is linked with a reduction in comorbid co...
journal_title:Diabetes & metabolism
pub_type: 杂志文章,评审
doi:
更新日期:2000-06-01 00:00:00