Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.

Abstract:

OBJECTIVE:Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes. RESEARCH DESIGN AND METHODS:We screened INS in 62 probands with MODY, 30 probands with suspected MODY, and 223 subjects from the Norwegian Childhood Diabetes Registry selected on the basis of autoantibody negativity or family history of diabetes. RESULTS:Among the MODY patients, we identified the INS mutation c.137G>A (R46Q) in a proband, his diabetic father, and a paternal aunt. They were diagnosed with diabetes at 20, 18, and 17 years of age, respectively, and are treated with small doses of insulin or diet only. In type 1 diabetic patients, we found the INS mutation c.163C>T (R55C) in a girl who at 10 years of age presented with ketoacidosis and insulin-dependent, GAD, and insulinoma-associated antigen-2 (IA-2) antibody-negative diabetes. Her mother had a de novo R55C mutation and was diagnosed with ketoacidosis and insulin-dependent diabetes at 13 years of age. Both had residual beta-cell function. The R46Q substitution changes an invariant arginine residue in position B22, which forms a hydrogen bond with the glutamate at A17, stabilizing the insulin molecule. The R55C substitution involves the first of the two arginine residues localized at the site of proteolytic processing between the B-chain and the C-peptide. CONCLUSIONS:Our findings extend the phenotype of INS mutation carriers and suggest that INS screening is warranted not only in neonatal diabetes, but also in MODY and in selected cases of type 1 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Molven A,Ringdal M,Nordbø AM,Raeder H,Støy J,Lipkind GM,Steiner DF,Philipson LH,Bergmann I,Aarskog D,Undlien DE,Joner G,Søvik O,Norwegian Childhood Diabetes Study Group.,Bell GI,Njølstad PR

doi

10.2337/db07-1467

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

1131-5

issue

4

eissn

0012-1797

issn

1939-327X

pii

db07-1467

journal_volume

57

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism.

    abstract:OBJECTIVE:Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with ho...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0787

    authors: Suliman SG,Stanik J,McCulloch LJ,Wilson N,Edghill EL,Misovicova N,Gasperikova D,Sandrikova V,Elliott KS,Barak L,Ellard S,Volpi EV,Klimes I,Gloyn AL

    更新日期:2009-12-01 00:00:00

  • Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes.

    abstract::Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrati...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1025

    authors: Michels AW,Landry LG,McDaniel KA,Yu L,Campbell-Thompson M,Kwok WW,Jones KL,Gottlieb PA,Kappler JW,Tang Q,Roep BO,Atkinson MA,Mathews CE,Nakayama M

    更新日期:2017-03-01 00:00:00

  • Modulation of glucocorticoid-induced GAD expression in pancreatic beta-cells by transcriptional activation of the GAD67 promoter and its possible effect on the development of diabetes.

    abstract::GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD) mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to be associated with the development of autoimmune diabetes. Hormonal changes through environmental stimuli are considered to influence the expression of the d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.9.2764

    authors: Kim KS,Kang Y,Choi SE,Kim JH,Kim HM,Sun B,Jun HS,Yoon JW

    更新日期:2002-09-01 00:00:00

  • Insulin B-chain reactive CD4+ regulatory T-cells induced by oral insulin treatment protect from type 1 diabetes by blocking the cytokine secretion and pancreatic infiltration of diabetogenic effector T-cells.

    abstract::The mechanism of protection from type 1 diabetes conferred by regulatory T-cells induced by oral insulin treatment of NOD mice is not well understood. We demonstrate that oral insulin feeding of NOD mice induces the function of insulin B-chain reactive CD4+ regulatory T-cells, which compete with diabetogenic effector ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.9.1720

    authors: Bergerot I,Arreaza GA,Cameron MJ,Burdick MD,Strieter RM,Chensue SW,Chakrabarti S,Delovitch TL

    更新日期:1999-09-01 00:00:00

  • A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure.

    abstract::Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. W...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.901

    authors: Tataranni PA,Baier L,Jenkinson C,Harper I,Del Parigi A,Bogardus C

    更新日期:2001-04-01 00:00:00

  • Hyperlipoproteinemia in streptozotocin-treated rats.

    abstract::In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.6.509

    authors: Bar-On H,Roheim PS,Eder HA

    更新日期:1976-06-01 00:00:00

  • Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.

    abstract:OBJECTIVE:Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary hu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0583

    authors: Bouzakri K,Austin R,Rune A,Lassman ME,Garcia-Roves PM,Berger JP,Krook A,Chibalin AV,Zhang BB,Zierath JR

    更新日期:2008-06-01 00:00:00

  • Involvement of cAMP/EPAC/TRPM2 activation in glucose- and incretin-induced insulin secretion.

    abstract::In pancreatic β-cells, closure of the ATP-sensitive K(+) (K(ATP)) channel is an initial process triggering glucose-stimulated insulin secretion. In addition, constitutive opening of background nonselective cation channels (NSCCs) is essentially required to effectively evoke depolarization as a consequence of K(ATP) ch...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1868

    authors: Yosida M,Dezaki K,Uchida K,Kodera S,Lam NV,Ito K,Rita RS,Yamada H,Shimomura K,Ishikawa SE,Sugawara H,Kawakami M,Tominaga M,Yada T,Kakei M

    更新日期:2014-10-01 00:00:00

  • Risk of diabetes in siblings and other relatives of IDDM subjects.

    abstract::The risk of insulin-dependent diabetes mellitus (IDDM) was examined in siblings of an unselected population (n = 194) of newly diagnosed diabetic individuals less than 30 yr old. From 1 July 1984 to 30 June 1987, diabetic subjects (proband) identified within a geographically defined area of southern Wisconsin were stu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.7.831

    authors: Allen C,Palta M,D'Alessio DJ

    更新日期:1991-07-01 00:00:00

  • Increase in simultaneous coexpression of naive and memory lymphocyte markers at diagnosis of IDDM.

    abstract::The monoclonal antibodies 2H4 (anti-CD45RA) and UCHL1 (anti-CD45RO) were used to subdivide the CD4 and CD8 T-cell subsets into naive and memory cells. The peripheral blood lymphocytes of 34 patients with recent-onset IDDM, 21 patients with long-standing IDDM, and healthy control subjects of similar age and sex were an...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.1.127

    authors: Smerdon RA,Peakman M,Hussain MJ,Alviggi L,Watkins PJ,Leslie RD,Vergani D

    更新日期:1993-01-01 00:00:00

  • Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

    abstract::Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is n...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.03.06.db05-0677

    authors: Sriwijitkamol A,Christ-Roberts C,Berria R,Eagan P,Pratipanawatr T,DeFronzo RA,Mandarino LJ,Musi N

    更新日期:2006-03-01 00:00:00

  • Longitudinal study on pubertal insulin resistance.

    abstract::Previous cross-sectional studies show that puberty is associated with a reduction in insulin sensitivity (S(I)), but no longitudinal studies have examined this change in detail. This study is a longitudinal study in 60 children (33 male and 27 female subjects; 32 Caucasian and 28 African-American) examined at Tanner s...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.11.2444

    authors: Goran MI,Gower BA

    更新日期:2001-11-01 00:00:00

  • Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism.

    abstract::Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. This review will address the biology, actions, and regulation of three adipocyte hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an emphasis...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.53.2007.s143

    authors: Havel PJ

    更新日期:2004-02-01 00:00:00

  • Control of blood glucose in experimental diabetes by means of a totally implantable insulin infusion device.

    abstract::Near-normal glucose tolerance tests in diabetic dogs were obtained during basal rate insulin infusions in restrained animals by use of extracorporeal infusion pumps and in conscious, unrestrained animals by means of implanted infusion pumps. Even better regulation of blood glucose in diabetic animals was obtained by t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.7.634

    authors: Blackshear PJ,Rohde TD,Grotting JC,Dorman FD,Perkins PR,Varco RL,Buchwald H

    更新日期:1979-07-01 00:00:00

  • A reduced-fat diet and aerobic exercise in Japanese Americans with impaired glucose tolerance decreases intra-abdominal fat and improves insulin sensitivity but not beta-cell function.

    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

    authors: Carr DB,Utzschneider KM,Boyko EJ,Asberry PJ,Hull RL,Kodama K,Callahan HS,Matthys CC,Leonetti DL,Schwartz RS,Kahn SE,Fujimoto WY

    更新日期:2005-02-01 00:00:00

  • Progression to type 2 diabetes characterized by moderate then rapid glucose increases.

    abstract:OBJECTIVE:The transition of an individual from normoglycemia to diabetes has generally been thought to involve either moderate or rapid changes in glucose over time, although few studies have analyzed these changes. We sought to determine whether a general pattern of glucose change exists in most individuals who become...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0053

    authors: Mason CC,Hanson RL,Knowler WC

    更新日期:2007-08-01 00:00:00

  • Effect of omega-3 fatty acids in diet of type I diabetic subjects on lipid values and hemorheological parameters.

    abstract::Twelve type I (insulin-dependent) diabetic subjects in stable metabolic control for at least 3 mo received a controlled diet containing 50% carbohydrate, 35% fat, and 15% protein. Calorie intake varied from 1800 to 2200 calories, depending on individual needs. Part of the polyunsaturated omega-6 fatty acids (omega 6FA...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.11.1412

    authors: Rillaerts EG,Engelmann GJ,Van Camp KM,De Leeuw I

    更新日期:1989-11-01 00:00:00

  • Selective unresponsiveness of pancreatic beta-cells to acute sulfonylurea stimulation during sulfonylurea therapy in NIDDM.

    abstract::Patients with non-insulin-dependent diabetes mellitus (NIDDM) who have chronic hyperglycemia lose acute incremental insulin responses to glucose but are able to briskly respond to other beta-cell secretagogues. To investigate whether this is a defect specific for glucose or represents a more general phenomenon, we mea...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.12.1314

    authors: Karam JH,Sanz N,Salamon E,Nolte MS

    更新日期:1986-12-01 00:00:00

  • The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells.

    abstract::To characterize the differentiation events that selectively target insulin-producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta signaling via mitogen-activated protein kinase (MAPK) and stress-activated protein kinase in 2 pancreatic endocrine cell lines. We studied the glucagon-secreting A...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.9.1468

    authors: Ammendrup A,Maillard A,Nielsen K,Aabenhus Andersen N,Serup P,Dragsbaek Madsen O,Mandrup-Poulsen T,Bonny C

    更新日期:2000-09-01 00:00:00

  • Insertion/deletion polymorphism of the ACE gene is associated with type 2 diabetes.

    abstract::In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, an...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.6.1986

    authors: Feng Y,Niu T,Xu X,Chen C,Li Q,Qian R,Wang G,Xu X

    更新日期:2002-06-01 00:00:00

  • The rat T-cell surface protein RT6 is associated with src family tyrosine kinases and generates an activation signal.

    abstract::RT6 is a glycosyl-phosphatidylinositol-linked surface molecule present on most mature rat T-cells. RT6+ T-cells can prevent the expression of autoimmune diabetes in the BB rat, but the mechanism is unknown. Because cross-linking of other glycosyl-phosphatidylinositol-linked T-cell proteins is known to activate T-cells...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.45.10.1419

    authors: Rigby MR,Bortell R,Greiner DL,Czech MP,Klarlund JK,Mordes JP,Rossini AA

    更新日期:1996-10-01 00:00:00

  • Glucose-induced accumulation of fructose-2,6-bisphosphate in pancreatic islets.

    abstract::Rat islets contain the acid-labile activator of phosphofructokinase, fructose-2,6-bisphosphate. The islet content in activator is higher in islets exposed to glucose (16.7 mM) than in islets deprived of glucose. The islets display fructose-6-phosphate, 2-kinase activity with a Km for fructose-6-phosphate close to 0.08...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.31.1.90

    authors: Malaisse WJ,Malaisse-Lagae F,Sener A

    更新日期:1982-01-01 00:00:00

  • Protein engineering strategies for sustained glucagon-like peptide-1 receptor-dependent control of glucose homeostasis.

    abstract:OBJECTIVE:We have developed a novel platform for display and delivery of bioactive peptides that links the biological properties of the peptide to the pharmacokinetic properties of an antibody. Peptides engineered in the MIMETIBODY platform have improved biochemical and biophysical properties that are quite distinct fr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-1775

    authors: Picha KM,Cunningham MR,Drucker DJ,Mathur A,Ort T,Scully M,Soderman A,Spinka-Doms T,Stojanovic-Susulic V,Thomas BA,O'Neil KT

    更新日期:2008-07-01 00:00:00

  • Effects of differing antecedent increases of plasma cortisol on counterregulatory responses during subsequent exercise in type 1 diabetes.

    abstract:OBJECTIVE:Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next-day exercise in type 1 diabetes. The aim of this study was to determine whether antecedent increase of plasma cortisol is a mechanism responsible for this finding. RESEARCH DESIGN AND METHODS:For this study, 22 ty...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db09-0382

    authors: Bao S,Briscoe VJ,Tate DB,Davis SN

    更新日期:2009-09-01 00:00:00

  • Inactivation of NF-κB p65 (RelA) in Liver Improves Insulin Sensitivity and Inhibits cAMP/PKA Pathway.

    abstract::The transcription factor nuclear factor-κB (NF-κB) mediates inflammation and stress signals in cells. To test NF-κB in the control of hepatic insulin sensitivity, we inactivated NF-κB in the livers of C57BL/6 mice through deletion of the p65 gene, which was achieved by crossing floxed-p65 and Alb-cre mice to generate ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0242

    authors: Ke B,Zhao Z,Ye X,Gao Z,Manganiello V,Wu B,Ye J

    更新日期:2015-10-01 00:00:00

  • Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose tolerance.

    abstract::Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic vesicle priming. We recently showed that Munc13-1 is expressed in rodent and human islet beta-cells and that its levels are reduced in islets of type 2 diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes to the abnor...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-1263

    authors: Kwan EP,Xie L,Sheu L,Nolan CJ,Prentki M,Betz A,Brose N,Gaisano HY

    更新日期:2006-05-01 00:00:00

  • Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell.

    abstract::Glucose controls islet beta-cell mass and function at least in part through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway downstream of insulin signaling. The Foxo proteins, transcription factors known in other tissues to be negatively regulated by Akt activation, affect proliferation and metabolism. In this st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-0678

    authors: Martinez SC,Cras-Méneur C,Bernal-Mizrachi E,Permutt MA

    更新日期:2006-06-01 00:00:00

  • Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival?

    abstract::There is growing interest in more widespread application of isolated islet transplantation for the treatment of type 1 diabetes; however, the sequelae of long-term islet residence within the liver are unknown. We report herein a consequence of intraportal islet transplantation, specifically the development of periport...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.7.1591

    authors: Markmann JF,Rosen M,Siegelman ES,Soulen MC,Deng S,Barker CF,Naji A

    更新日期:2003-07-01 00:00:00

  • KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression.

    abstract::Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is a promising strategy for combating obesity. Here, we find that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1901

    authors: Chou CF,Lin YY,Wang HK,Zhu X,Giovarelli M,Briata P,Gherzi R,Garvey WT,Chen CY

    更新日期:2014-09-01 00:00:00

  • Myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38α MAPK during insulin resistance.

    abstract::Cardiac failure is a major cause of death in patients with type 2 diabetes, but the molecular mechanism that links diabetes to heart failure remains unclear. Insulin resistance is a hallmark of type 2 diabetes, and insulin receptor substrates 1 and 2 (IRS1 and IRS2) are the major insulin-signaling components regulatin...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0095

    authors: Qi Y,Xu Z,Zhu Q,Thomas C,Kumar R,Feng H,Dostal DE,White MF,Baker KM,Guo S

    更新日期:2013-11-01 00:00:00