Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes.

Abstract:

BACKGROUND:Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet beta-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell self-tolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat. METHODS:The expression of the mammalian insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP) rats. RESULTS:RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA was observed in more than 80% of BBDP thymi. The absence of detectable Igf2 transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were detected in all BBDP brains and livers examined. Using a specific immunoradiometric assay, the concentration of thymic IGF-2 protein was significantly lower in BBDP than in BBDR rats (p<0.01). CONCLUSIONS:The present study suggests an association between the emergence of autoimmune diabetes and a defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect in gene expression could contribute both to the lymphopenia of these rats (by impaired T-cell development) and the absence of central T-cell self-tolerance of the insulin hormone family (by defective negative selection of self-reactive T-cells).

journal_name

Diabetes Metab Res Rev

authors

Kecha-Kamoun O,Achour I,Martens H,Collette J,Lefebvre PJ,Greiner DL,Geenen V

doi

10.1002/dmrr.182

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

146-52

issue

2

eissn

1520-7552

issn

1520-7560

pii

10.1002/dmrr.182

journal_volume

17

pub_type

杂志文章
  • Prevalence of undiagnosed dysglycemia in an emergency department observation unit.

    abstract:BACKGROUND:The proposed 2015 US Preventive Services Task Force guidelines recommend diabetes screening for individuals ≥45 years or demonstrating other risk factors for dysglycemia. Still, many patients with dysglycemia remain undiagnosed, and opportunities for early intervention are lost. METHODS:To test novel approa...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2674

    authors: Silverman RA,Schleicher MG,Valente CJ,Kim M,Romanenko Y,Schulman RC,Tiberio A,Greenblatt B,Rentala M,Salvador-Kelly AV,Kwon NS,Jornsay DL

    更新日期:2016-01-01 00:00:00

  • A case-control study: The association of serum paraoxonase 1 activity and concentration with the development of type 2 diabetes mellitus.

    abstract:BACKGROUND:A longitudinal study assessed serum paraoxonase 1 (PON1) activity and concentration as affected by age and as associated with the development of type 2 diabetes (T2D). PON1's recently established physiological function is the hydrolysis of lipolactones in oxidized LDL particles. METHODS:Serum samples and cl...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2967

    authors: Crow JA,Meek EC,Wills RW,Chambers JE

    更新日期:2018-03-01 00:00:00

  • Predicting ulcer-free survival using the discriminative value of screening test locations.

    abstract:BACKGROUND:Current guidelines recommend screening the feet of diabetic subjects with a 10-g monofilament or tuning fork. We investigated which tests and locations on the feet have the best predictive value regarding 1-year ulcer-free survival in diabetic subjects participating in the prospective Rotterdam Diabetic Foot...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.3119

    authors: Rinkel WD,van der Oest MJW,Dijkstra DA,Castro Cabezas M,Coert JH

    更新日期:2019-03-01 00:00:00

  • Vitamin D deficiency is associated with painful diabetic neuropathy.

    abstract:BACKGROUND:The aetiology of painful diabetic neuropathy is unclear. We have evaluated vitamin D levels in diabetic patients with and without painful neuropathy. METHODS:Forty-three patients with type 1 diabetes and painless (DPN) (n = 20) or painful (PDN) (n = 23) neuropathy and 14 non-diabetic healthy control subject...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.3361

    authors: Alam U,Petropoulos IN,Ponirakis G,Ferdousi M,Asghar O,Jeziorska M,Marshall A,Boulton AJM,Efron N,Malik RA

    更新日期:2021-01-01 00:00:00

  • Preventing diabetes in women with gestational diabetes.

    abstract::The immediate consequences of gestational diabetes on pregnancy are well known but the complications decades later for the mother and child are just now emerging. This trio of papers discuss the long-term consequences of gestational diabetes, the importance of screening this high risk group of women for type 2 diabete...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 社论

    doi:10.1002/dmrr.2280

    authors: Feig D

    更新日期:2012-05-01 00:00:00

  • Positive effects of GLP-1 receptor activation with liraglutide on pancreatic islet morphology and metabolic control in C57BL/KsJ db/db mice with degenerative diabetes.

    abstract:BACKGROUND:Stable glucagon-like peptide-1 (GLP-1) mimetics, such as the GLP-1 analogue liraglutide, are approved for treatment of type 2 diabetes. GLP-1 has a spectrum of anti-diabetic effects that are of possible utility in the treatment of more severe forms of diabetes. METHODS:The present study has evaluated the ef...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2608

    authors: Moffett RC,Patterson S,Irwin N,Flatt PR

    更新日期:2015-03-01 00:00:00

  • New developments in the biomechanics of the diabetic foot.

    abstract::Biomechanical issues are now widely recognized as being important in the treatment of diabetic foot disease. The purpose of the present review is to identify advances that have occurred since the previous International Conference on the Diabetic Foot in 1995 in the understanding of foot biomechanics in relation to dia...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,评审

    doi:10.1002/1520-7560(200009/10)16:1+<::aid-dmrr130>3.

    authors: Cavanagh PR,Ulbrecht JS,Caputo GM

    更新日期:2000-09-01 00:00:00

  • Ceftaroline fosamil for treatment of diabetic foot infections: the CAPTURE study experience.

    abstract:BACKGROUND:To ascertain which demographic, clinical, and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing Clinical Assessment Program and Teflaro® Utilization Registry study data of patients treated with ceftaroline fosamil. M...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,多中心研究

    doi:10.1002/dmrr.2624

    authors: Lipsky BA,Cannon CM,Ramani A,Jandourek A,Calmaggi A,Friedland HD,Goldstein EJ

    更新日期:2015-05-01 00:00:00

  • Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case-control study.

    abstract:BACKGROUND:The adaptive immune system is involved in type 2 diabetes mellitus (T2DM), indicating the presence of unidentified autoantibodies that might be useful biomarkers for emerging immunomodulatory therapy. A prior microarray study with a small number of participants suggested the association of novel autoantibodi...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2922

    authors: Chang DC,Piaggi P,Hanson RL,Knowler WC,Bogardus C,Krakoff J

    更新日期:2017-11-01 00:00:00

  • Regulation of muscle malonyl-CoA levels in the nutritionally insulin-resistant desert gerbil, Psammomys obesus.

    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

    authors: Shafrir E,Ziv E,Saha AK,Ruderman NB

    更新日期:2002-05-01 00:00:00

  • A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell-related glycolipids, sulfatide and β-galactosylceramide.

    abstract:BACKGROUND:T1DM is a T-cell-mediated autoimmune disease targeting insulin-producing beta-cells. Multiple factors may contribute to the development of T1DM. Among these, the metabolic state of beta-cells and pro-inflammatory cytokines, produced by infiltrating immune cells, have been implicated in the precipitation of T...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.1134

    authors: Osterbye T,Funda DP,Fundová P,Månsson JE,Tlaskalová-Hogenová H,Buschard K

    更新日期:2010-11-01 00:00:00

  • Birth weight influences the clinical phenotype and the metabolic control of patients with type 1 diabetes (T1D).

    abstract:BACKGROUND:High birth weight has been related to an increased risk of type 1 diabetes (T1D), while suboptimal birth weight (both high and low) has been related to obesity, insulin resistance and type 2 diabetes. Insulin resistance, as a consequence of poor metabolic control, has been described in T1D patients. The aims...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2361

    authors: Benevento D,Bizzarri C,Patera IP,Ravà L,Schiaffini R,Ciampalini P,Cianfarani S,Cappa M

    更新日期:2013-01-01 00:00:00

  • Advanced glycosylation end products (AGEs), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) in patients with type 2 diabetes mellitus.

    abstract:BACKGROUND:Advanced glycosylation end product (AGE) formation is a major mechanism for the development of complications in diabetes, and the possible roles of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are not clearly established. METHODS:We examined the associations of AGEs, free IGF-I a...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/(sici)1520-7560(200003/04)16:2<106::aid-dm

    authors: Garay-Sevilla ME,Nava LE,Malacara JM,Wróbel K,Wróbel K,Pérez U

    更新日期:2000-03-01 00:00:00

  • Diabetes and microvascular pathophysiology: role of epidermal growth factor receptor tyrosine kinase.

    abstract::Type 2 diabetes is responsible for the increased prevalence of ischaemic heart disease, generally related to coronary artery disease, which is associated with increased morbidity and death in diabetic patients. Epidermal growth factor receptor (EGFR) tyrosine kinase, one of the many factors involved in cell growth and...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,评审

    doi:10.1002/dmrr.1050

    authors: Matrougui K

    更新日期:2010-01-01 00:00:00

  • Effects of sodium-glucose cotransporter (SGLT) inhibitors in addition to insulin therapy on glucose control and safety outcomes in adults with type 1 diabetes: A meta-analysis of randomized controlled trials.

    abstract::Sodium-glucose cotransporter (SGLT) inhibitors added to insulin therapy have been proposed as treatment strategy for type 1 diabetes (T1D). We thus conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of this combination in T1D. We searched the PubMed, EMBASE, and...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,meta分析,评审

    doi:10.1002/dmrr.3169

    authors: Lu J,Tang L,Meng H,Zhao J,Liang Y

    更新日期:2019-10-01 00:00:00

  • A systematic review of the effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral arterial disease.

    abstract::In several large recent observational studies, peripheral arterial disease (PAD) was present in up to 50% of the patients with a diabetic foot ulcer and was an independent risk factor for amputation. The International Working Group on the Diabetic Foot therefore established a multidisciplinary working group to evaluat...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,评审

    doi:10.1002/dmrr.2249

    authors: Hinchliffe RJ,Andros G,Apelqvist J,Bakker K,Friederichs S,Lammer J,Lepantalo M,Mills JL,Reekers J,Shearman CP,Valk G,Zierler RE,Schaper NC

    更新日期:2012-02-01 00:00:00

  • Induction of long-term normoglycemia without medication in Korean type 2 diabetes patients after continuous subcutaneous insulin infusion therapy.

    abstract:BACKGROUND:Our previous studies showed that some Korean type 2 diabetic patients could maintain long-term normal blood glucose control without any medication, referred to as remission after a certain period of normalization of blood glucose level by continuous subcutaneous insulin infusion (CSII) treatment. In this stu...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.343

    authors: Park S,Choi SB

    更新日期:2003-03-01 00:00:00

  • Global DNA methylation as a possible biomarker for diabetic retinopathy.

    abstract:BACKGROUND:We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. METHODS:The 5-methylcytosine content was assessed by reversed-phase ...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2584

    authors: Maghbooli Z,Hossein-nezhad A,Larijani B,Amini M,Keshtkar A

    更新日期:2015-02-01 00:00:00

  • Coincident diabetes mellitus and primary hyperparathyroidism.

    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

    authors: Taylor WH,Khaleeli AA

    更新日期:2001-05-01 00:00:00

  • The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes.

    abstract:BACKGROUND:The aim of the study is to assess the relationship between the shape of plasma glucose concentration during the OGTT and future risk for T2DM. METHODS:2445 non-diabetic subjects from the Botnia study received an OGTT at baseline and after 7-8 years of follow-up. RESULTS:NGT and IFG subjects who returned th...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.1084

    authors: Abdul-Ghani MA,Lyssenko V,Tuomi T,Defronzo RA,Groop L

    更新日期:2010-05-01 00:00:00

  • Overexpression of ZAC impairs glucose-stimulated insulin translation and secretion in clonal pancreatic beta-cells.

    abstract:BACKGROUND:ZAC (Zinc finger protein that regulates apoptosis and cell-cycle arrest) is a candidate gene for transient neonatal diabetes mellitus (TNDM). This condition involves severe insulin deficiency at birth that reverses over weeks or months but may relapse with diabetes recurring in later life. ZAC overexpression...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.2325

    authors: Du X,Ounissi-Benkalha H,Loder MK,Rutter GA,Polychronakos C

    更新日期:2012-11-01 00:00:00

  • The decrement in circulating endothelial progenitor cells (EPCs) in type 2 diabetes is independent of the severity of the hypoadiponectemia.

    abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a decreased level of circulating endothelial progenitor cells (EPCs) and adiponectin. Experimental studies suggest a potential link between hypoadiponectinaemia and the depletion of the EPC level. This study investigated the relationships between adiponectin l...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.1159

    authors: Li M,Ho JC,Lai KW,Au KK,Xu A,Cheung BM,Lam KS,Tse HF

    更新日期:2011-02-01 00:00:00

  • Periodontal risk markers in children and adolescents with type 1 diabetes: A systematic review and meta-analysis.

    abstract:BACKGROUND:Periodontal disease is a frequent complication of diabetes in adults, and both conditions are associated with systemic inflammatory states. This systematic review and meta-analysis was conducted to establish the relative severity of periodontal disease risk markers in children and adolescents with type 1 dia...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,评审

    doi:10.1002/dmrr.3368

    authors: Jensen E,Allen G,Bednarz J,Couper J,Peña A

    更新日期:2021-01-01 00:00:00

  • The development of a World Health Organisation international standard for islet cell antibodies: the aims and design of an international collaborative study.

    abstract::Islet cell antibodies (ICA) are a specific marker for Type 1 (insulin-dependent) diabetes mellitus. ICA are found in the serum of over 80% of newly diagnosed patients and the levels of ICA are directly of prognostic value. Standardisation of ICA and the uniform reporting of ICA levels in international units is critica...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/(sici)1520-7560(199901/02)15:1<72::aid-dmr

    authors: Mire-Sluis AR,Das RG,Lernmark A

    更新日期:1999-01-01 00:00:00

  • Immune regulation by CTLA-4--relevance to autoimmune diabetes in a transgenic mouse model.

    abstract:BACKGROUND:The importance of cytotoxic T lymphocyte antigen-4 (CTLA-4) in immune regulation is unquestioned, yet a precise understanding of which cells express it, and how it mediates immune inhibitory function, is lacking. Regulatory T cells are known to constitutively express CTLA-4 intracellularly, whereas conventio...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.1277

    authors: Wang CJ,Schmidt EM,Attridge K,Kenefeck R,Wardzinski L,Chamberlain JL,Soulier A,Clough LE,Manzotti CN,Narendran P,Walker LS

    更新日期:2011-11-01 00:00:00

  • Diagnosis of infection in the foot in diabetes: a systematic review.

    abstract:BACKGROUND:Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potentially mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS:In June 2018, we searche...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.3281

    authors: Senneville É,Lipsky BA,Abbas ZG,Aragón-Sánchez J,Diggle M,Embil JM,Kono S,Lavery LA,Malone M,van Asten SA,Urbančič-Rovan V,Peters EJG

    更新日期:2020-03-01 00:00:00

  • Serum protein patterns in newly diagnosed type 2 diabetes mellitus--influence of diabetic environment and family history of diabetes.

    abstract:BACKGROUND:Individuals with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM) represent heterogeneous groups with differences in beta-cell function and genetic background. The aim of the present study was to compare serum protein profiles of NGT and T2DM individuals and determine the influence of the g...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.789

    authors: Sundsten T,Ostenson CG,Bergsten P

    更新日期:2008-02-01 00:00:00

  • A practical approach to the clinical challenges in initiation of basal insulin therapy in people with type 2 diabetes.

    abstract::Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of gly...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章,评审

    doi:10.1002/dmrr.3418

    authors: Forst T,Choudhary P,Schneider D,Linetzky B,Pozzilli P

    更新日期:2020-10-23 00:00:00

  • Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon-like peptide 1.

    abstract:BACKGROUND:Variants in TCF7L2 have been associated with the age at onset of type 2 diabetes in Mexican Americans. However, there is a lack of data on this relationship in Caucasians. Furthermore, risk alleles in TCF7L2 have been suggested to account for decreased conversion of proinsulin to insulin and decreased expres...

    journal_title:Diabetes/metabolism research and reviews

    pub_type: 杂志文章

    doi:10.1002/dmrr.1194

    authors: Silbernagel G,Renner W,Grammer TB,Hügl SR,Bertram J,Kleber ME,Hoffmann MM,Winkelmann BR,März W,Boehm BO

    更新日期:2011-07-01 00:00:00

  • Questions on therapy with DPP-4 inhibitors and bone homeostasis.

    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

    authors: Napoli N

    更新日期:2014-03-01 00:00:00