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
  • Mitochondrial respiratory capacity and content are normal in young insulin-resistant obese humans.

    abstract::Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in hum...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0940

    authors: Fisher-Wellman KH,Weber TM,Cathey BL,Brophy PM,Gilliam LA,Kane CL,Maples JM,Gavin TP,Houmard JA,Neufer PD

    更新日期:2014-01-01 00:00:00

  • Altered lysosomal glycohydrolase activities in juvenile diabetes mellitus.

    abstract::Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.5.420

    authors: Bomback FM,Nakagawa S,Kumin S,Nitowsky HM

    更新日期:1976-05-01 00:00:00

  • Adiponectin multimeric complexes and the metabolic syndrome trait cluster.

    abstract::Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., r...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:

    authors: Lara-Castro C,Luo N,Wallace P,Klein RL,Garvey WT

    更新日期:2006-01-01 00:00:00

  • Gene silencing of phogrin unveils its essential role in glucose-responsive pancreatic beta-cell growth.

    abstract:OBJECTIVE:Phogrin and IA-2, autoantigens in insulin-dependent diabetes, have been shown to be involved in insulin secretion in pancreatic beta-cells; however, implications at a molecular level are confusing from experiment to experiment. We analyzed biological functions of phogrin in beta-cells by an RNA interference t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-0970

    authors: Torii S,Saito N,Kawano A,Hou N,Ueki K,Kulkarni RN,Takeuchi T

    更新日期:2009-03-01 00:00:00

  • Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines.

    abstract::Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1429

    authors: Mastrandrea LD,Sessanna SM,Laychock SG

    更新日期:2005-05-01 00:00:00

  • Glucosylated collagen is antigenic.

    abstract::Sera from rats inoculated with in vitro glucosylated rat skin acid-soluble collagen were evaluated for specific antibody response using the enzyme-linked immunosorbent assay. The data indicate that the altered protein is capable of eliciting the production of antibodies, but unmodified collagen is not. The specificity...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.12.1182

    authors: Bassiouny AR,Rosenberg H,McDonald TL

    更新日期:1983-12-01 00:00:00

  • Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

    abstract::We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1334

    authors: Lee HY,Lee JS,Alves T,Ladiges W,Rabinovitch PS,Jurczak MJ,Choi CS,Shulman GI,Samuel VT

    更新日期:2017-08-01 00:00:00

  • Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    abstract::Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0291

    authors: Schafer MJ,White TA,Evans G,Tonne JM,Verzosa GC,Stout MB,Mazula DL,Palmer AK,Baker DJ,Jensen MD,Torbenson MS,Miller JD,Ikeda Y,Tchkonia T,van Deursen JM,Kirkland JL,LeBrasseur NK

    更新日期:2016-06-01 00:00:00

  • Development and function of diabetogenic T-cells in B-cell-deficient nonobese diabetic mice.

    abstract::Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.763

    authors: Chiu PP,Serreze DV,Danska JS

    更新日期:2001-04-01 00:00:00

  • PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.

    abstract::The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functi...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.47.4.507

    authors: Spiegelman BM

    更新日期:1998-04-01 00:00:00

  • Immunochemical characterization of anti-islet cell surface monoclonal antibody from nonobese diabetic mice.

    abstract::We have produced a monoclonal antibody 3A4 to the surface of islet cells by fusing spleen lymphocytes from nonobese diabetic (NOD) mice. To identify the molecular weight of specific target antigens reacting with 3A4, 125I-surface-labeled In-111 insulinoma cells were solubilized and extracts were absorbed with 3A4, and...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.5.517

    authors: Hari J,Yokono K,Yonezawa K,Amano K,Yaso S,Shii K,Imamura Y,Baba S

    更新日期:1986-05-01 00:00:00

  • Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes.

    abstract::Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine the MT-I+II-mediated ant...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,收录出版

    doi:10.2337/diabetes.54.11.3089

    authors: Scheede-Bergdahl C,Penkowa M,Hidalgo J,Olsen DB,Schjerling P,Prats C,Boushel R,Dela F

    更新日期:2005-11-01 00:00:00

  • Pericyte Bridges in Homeostasis and Hyperglycemia.

    abstract::Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0471

    authors: Corliss BA,Ray HC,Doty RW,Mathews C,Sheybani N,Fitzgerald K,Prince R,Kelly-Goss MR,Murfee WL,Chappell J,Owens GK,Yates PA,Peirce SM

    更新日期:2020-07-01 00:00:00

  • Characterization of human DNA topoisomerase II as an autoantigen recognized by patients with IDDM.

    abstract::Autoantibodies against several cytoplasmic autoantigens such as glutamic acid decarboxylase, heat shock protein 65, insulin, and carboxypeptidase H have been identified in the sera of patients with IDDM. To investigate whether type II DNA topoisomerase (TopII) is an autoantigen in IDDM patients, we have constructed a ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.45.4.408

    authors: Chang YH,Hwang J,Shang HF,Tsai ST

    更新日期:1996-04-01 00:00:00

  • Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement.

    abstract::Akt is critical in insulin-induced metabolism of glucose and lipids. To investigate functions induced by hepatic Akt activation, a constitutively active Akt, NH(2)-terminally myristoylation signal-attached Akt (myr-Akt), was overexpressed in the liver by injecting its adenovirus into mice. Hepatic myr-Akt overexpressi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.12.2905

    authors: Ono H,Shimano H,Katagiri H,Yahagi N,Sakoda H,Onishi Y,Anai M,Ogihara T,Fujishiro M,Viana AY,Fukushima Y,Abe M,Shojima N,Kikuchi M,Yamada N,Oka Y,Asano T

    更新日期:2003-12-01 00:00:00

  • Progression from insulitis to beta-cell destruction in NOD mouse requires L3T4+ T-lymphocytes.

    abstract::The identity of the cells responsible for beta-cell destruction in type I (insulin-dependent) diabetes is still uncertain. L3T4+ T-lymphocytes have a role in the initiation of insulitis and in damaging transplanted allogeneic islets in nonobese diabetic (NOD) mice. The role of L3T4+ T-lymphocytes in destruction of bet...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.8.1108

    authors: Charlton B,Mandel TE

    更新日期:1988-08-01 00:00:00

  • Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice.

    abstract::Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-1188

    authors: Zang M,Xu S,Maitland-Toolan KA,Zuccollo A,Hou X,Jiang B,Wierzbicki M,Verbeuren TJ,Cohen RA

    更新日期:2006-08-01 00:00:00

  • Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study.

    abstract::We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.2.202

    authors: Singer DE,Nathan DM,Anderson KM,Wilson PW,Evans JC

    更新日期:1992-02-01 00:00:00

  • A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice.

    abstract::In this article, we report on a nonobese C57BL/6 (B6) mouse model of NIDDM named Akita mouse, characterized by early age onset and autosomal dominant mode of inheritance. At 7 weeks of age, the mean morning blood glucose levels (mmol/l) under ad libitum feeding conditions were significantly higher (P < 0.01, analysis ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.5.887

    authors: Yoshioka M,Kayo T,Ikeda T,Koizumi A

    更新日期:1997-05-01 00:00:00

  • Effects of ponalrestat, an aldose reductase inhibitor, on neutrophil killing of Escherichia coli and autonomic function in patients with diabetes mellitus.

    abstract::In diabetic subjects, polyol pathway activity might inhibit neutrophil function and cause nerve damage. The effects of ponalrestat, an aldose reductase inhibitor, were assessed on neutrophil intracellular killing of Escherichia coli and on autonomic function in diabetic subjects in a randomized double-blind, placebo-c...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.42.2.336

    authors: Boland OM,Blackwell CC,Clarke BF,Ewing DJ

    更新日期:1993-02-01 00:00:00

  • Leptin accelerates autoimmune diabetes in female NOD mice.

    abstract::We have recently shown that leptin, the product of the obese gene, can directly influence T-cell function. In the work presented here, we explored the role of leptin in the development of spontaneous autoimmunity in the nonobese diabetic (NOD) mouse, an animal model for the study of human insulin-dependent diabetes me...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.5.1356

    authors: Matarese G,Sanna V,Lechler RI,Sarvetnick N,Fontana S,Zappacosta S,La Cava A

    更新日期:2002-05-01 00:00:00

  • Amelioration of hypoglycemia in a patient with malignant insulinoma during the development of the ectopic ACTH syndrome.

    abstract::A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to h...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.6.600

    authors: Sadoff L,Gordon J,Goldman S

    更新日期:1975-06-01 00:00:00

  • Endoplasmic reticulum stress and the development of diabetes: a review.

    abstract::The early steps of insulin biosynthesis occur in the endoplasmic reticulum (ER), and the beta-cell has a highly developed and active ER. All cells regulate the capacity of their ER to fold and process client proteins and they adapt to an imbalance between client protein load and folding capacity (so-called ER stress)....

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.51.2007.s455

    authors: Harding HP,Ron D

    更新日期:2002-12-01 00:00:00

  • Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study.

    abstract:OBJECTIVE:This study aimed to estimate the current cumulative risk of end-stage renal disease (ESRD) due to diabetic nephropathy in a large, nationwide, population-based prospective type 1 diabetes cohort and specifically study the effects of sex and age at onset. RESEARCH DESIGN AND METHODS:In Sweden, all incident ca...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1744

    authors: Möllsten A,Svensson M,Waernbaum I,Berhan Y,Schön S,Nyström L,Arnqvist HJ,Dahlquist G,Swedish Childhood Diabetes Study Group.,Diabetes Incidence Study in Sweden.,Swedish Renal Registry.

    更新日期:2010-07-01 00:00:00

  • Preservation of morphology, insulin biosynthesis, and insulin release in cryopreserved human fetal pancreas.

    abstract::Human fetal pancreatic glands were obtained from 12 consecutive prostaglandin-induced abortions. Explants cultured for 1 day were frozen at 0.3 degree C/min in a 1 M DMSO-containing medium and stored at -196 degrees C. After storage for 3-4 mo the frozen material was rapidly thawed and cultured 1 day before being test...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.31.3.238

    authors: Sandler S,Andersson A,Hellerström C,Petersson B,Swenne I,Björkén C,Groth CG

    更新日期:1982-03-01 00:00:00

  • Mechanisms Underlying Absent Training-Induced Improvement in Insulin Action in Lean, Hyperandrogenic Women With Polycystic Ovary Syndrome.

    abstract::Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control (CON) women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle, improving glucose uptake and metabolism in both healthy individuals and patients with type 2 diabetes. In...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db20-0062

    authors: Hansen SL,Bojsen-Møller KN,Lundsgaard AM,Hendrich FL,Nilas L,Sjøberg KA,Hingst JR,Serup AK,Olguín CH,Carl CS,Wernblad LF,Henneberg M,Lustrup KM,Hansen C,Jensen TE,Madsbad S,Wojtaszewski JFP,Richter EA,Kiens B

    更新日期:2020-11-01 00:00:00

  • Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated.

    abstract::In an effort to better understand the phenomenon of lipotoxicity in human beta-cells, we evaluated the effects of 48-h preculture with 1.0 or 2.0 mmol/l free fatty acid (FFA) (2:1 oleate to palmitate) on the function and survival of isolated human islets and investigated some of the possible mechanisms. Compared with ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.5.1437

    authors: Lupi R,Dotta F,Marselli L,Del Guerra S,Masini M,Santangelo C,Patané G,Boggi U,Piro S,Anello M,Bergamini E,Mosca F,Di Mario U,Del Prato S,Marchetti P

    更新日期:2002-05-01 00:00:00

  • Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age.

    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

    authors: Kallionpää H,Somani J,Tuomela S,Ullah U,de Albuquerque R,Lönnberg T,Komsi E,Siljander H,Honkanen J,Härkönen T,Peet A,Tillmann V,Chandra V,Anagandula MK,Frisk G,Otonkoski T,Rasool O,Lund R,Lähdesmäki H,Knip M,Lahes

    更新日期:2019-10-01 00:00:00

  • Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes.

    abstract::Although decreased levels of circulating insulinlike growth factor I (IGF-I) and hepatic IGF-I mRNA in diabetic animal models support a role for insulin in IGF-I regulation, it has been difficult to study the effects of insulin in vitro. Few immortal cell lines exhibit hormone-responsive production of IGF-I, and studi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.11.1525

    authors: Phillips LS,Goldstein S,Pao CI

    更新日期:1991-11-01 00:00:00

  • Quantification of collagen in renal glomeruli isolated from human nondiabetic and diabetic kidneys.

    abstract::Previous studies of diabetic renovascular complications have measured morphologic changes in relatively few glomerular vessels by electron microscopy. The present study samples 20,000 to 80,000 glomeruli from each of ten nondiabetic and ten diabetic age- and sex-matched subjects. Glomeruli were isolated and fractionat...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.12.1057

    authors: Klein L,Butcher DL,Sudilovsky O,Kikkawa R,Miller M

    更新日期:1975-12-01 00:00:00