A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

Abstract:

:ATP-sensitive potassium (K[ATP]) channels are an essential component of glucose-dependent insulin secretion in pancreatic islet beta-cells. These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family. Mutations in the SUR1 subunit are associated with familial hyperinsulinism (HI) (MIM:256450), an inherited disorder characterized by hyperinsulinism in the neonate. Since the Kir6.2 gene maps to human chromosome 11p15.1 (1,2), which also encompasses a locus for HI, we screened the Kir6.2 gene for the presence of mutations in 78 HI probands by single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses. A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation. The identification of an HI patient homozygous for the Kir6.2/Y12X allele affords an opportunity to observe clinical features associated with mutations resulting in an absence of Kir6.2. These data provide evidence that mutations in the Kir6.2 subunit of the islet beta-cell K(ATP) channel are associated with the HI phenotype and also suggest that the majority of HI cases are not attributable to mutations in the coding region of the Kir6.2 gene.

journal_name

Diabetes

journal_title

Diabetes

authors

Nestorowicz A,Inagaki N,Gonoi T,Schoor KP,Wilson BA,Glaser B,Landau H,Stanley CA,Thornton PS,Seino S,Permutt MA

doi

10.2337/diab.46.11.1743

subject

Has Abstract

pub_date

1997-11-01 00:00:00

pages

1743-8

issue

11

eissn

0012-1797

issn

1939-327X

journal_volume

46

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Therapeutic modulation of growth-promoting activity in platelets from diabetics.

    abstract::Proliferation of vascular smooth muscle is thought to be involved in the major diabetic complication atherosclerosis. We have previously reported an increase of growth-promoting activity (GA) in platelets from insulin-dependent diabetics. In this study, GA was measured in the platelet extract (PE) from eight diabetic ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.5.667

    authors: Sugimoto H,Franks DJ,Lecavalier L,Chiasson JL,Hamet P

    更新日期:1987-05-01 00:00:00

  • The size of the loading dose as an important determinant of the results of the oral glucose tolerance test: a study in subjects with slightly impaired glucose tolerance.

    abstract::In the oral glucose tolerance test (OGTT), divergent doses of glucose remain in use by virtue of the prevailing conviction that the size of the loading dose hardly affects the outcome of the test. We compared the results of OGTTs with 100-gm. and 50-gm. loads in 85 patients, who were selected for slightly impaired glu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.27.1.42

    authors: de Nobel E,van't Laar A

    更新日期:1978-01-01 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

  • Prospective study of predictors of beta-cell survival in type I diabetes.

    abstract::We conducted a prospective study to describe the course of the pancreatic beta-cell function from the time of clinical diagnosis of insulin-dependent (type I) diabetes to determine whether DR type, presence of islet cell antibodies (ICA), presence of insulin antibodies (IA), age at onset, and sex could help in the pre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.7.920

    authors: Schiffrin A,Suissa S,Poussier P,Guttmann R,Weitzner G

    更新日期:1988-07-01 00:00:00

  • Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics.

    abstract::Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow c...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.5.466

    authors: Williams G,Pickup J,Clark A,Bowcock S,Cooke E,Keen H

    更新日期:1983-05-01 00:00:00

  • Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice.

    abstract::Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.2.376

    authors: Masaki T,Yoshimatsu H,Chiba S,Watanabe T,Sakata T

    更新日期:2001-02-01 00:00:00

  • Hyperglycemia and beta-cell adaptation during prolonged somatostatin infusion with glucagon replacement in man.

    abstract::To assess the relationship between beta-cell function and the level and duration of hyperglycemia during generalized beta-cell impairment, we studied the effects of acute and prolonged infusion of somatostatin in seven normal men. Twenty minutes after beginning an acute infusion of somatostatin (200 microgram/h) plus ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.10.943

    authors: Ward WK,Halter JB,Best JD,Beard JC,Porte D Jr

    更新日期:1983-10-01 00:00:00

  • A new murine model of islet xenograft rejection: graft destruction is dependent on a major histocompatibility-specific interaction between T-cells and macrophages.

    abstract::A new murine model of porcine islet-like cell cluster (ICC) xenograft rejection, avoiding interference of unspecific inflammation, was introduced and used to investigate rejection mechanisms. Athymic (nu/nu) mice were transplanted with syngeneic, allogeneic, or xenogeneic islets under the kidney capsule. After the ori...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.5.1111

    authors: Schmidt P,Krook H,Maeda A,Korsgren O,Benda B

    更新日期:2003-05-01 00:00:00

  • Histologic differentiation of human fetal pancreatic explants transplanted into nude mice.

    abstract::The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the ti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.12.1180

    authors: Tuch BE,Ng AB,Jones A,Turtle JR

    更新日期:1984-12-01 00:00:00

  • Immunohistochemical localization of aldose reductase. II. Rat eye and kidney.

    abstract::Aldose reductase (AR) was purified from rat seminal vesicles. Specific antibodies to this enzyme were prepared in rabbits and were used in the unlabeled antibody-enzyme (PAP) technique to localize AR in a number of tissues known to be sites of diabetic lesions. AR was localized in the following structures in the eye: ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.6.450

    authors: Ludvigson MA,Sorenson RL

    更新日期:1980-06-01 00:00:00

  • Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

    abstract::Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesized that the MGO scavenge...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0933

    authors: Li H,O'Meara M,Zhang X,Zhang K,Seyoum B,Yi Z,Kaufman RJ,Monks TJ,Wang JM

    更新日期:2019-06-01 00:00:00

  • Reduced levels of mRNA encoding endoskeletal and growth-associated proteins in sensory ganglia in experimental diabetes.

    abstract::This study investigated changes in levels of mRNAs encoding the three neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal root ganglia of control and streptozocin-induced diabetic rats. After 8 weeks of diabetes...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.1.25

    authors: Mohiuddin L,Fernyhough P,Tomlinson DR

    更新日期:1995-01-01 00:00:00

  • Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.

    abstract:OBJECTIVE:White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0929

    authors: Cheng Y,Meng Q,Wang C,Li H,Huang Z,Chen S,Xiao F,Guo F

    更新日期:2010-01-01 00:00:00

  • Insulin sensitivity of isolated perfused rat liver.

    abstract::The responsiveness of the isolated perfused rat liver to different metabolic effects of insulin was investigated during recycling perfusion. Infusion of porcine insulin at rates of 6, 9, 16 and 33 mU/hr. resulted in stable perfusate insulin levels averaging 41, 72, 120 and 229 muU/ml., respectively. Since the portal v...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.2.225

    authors: Mondon CE,Dolkas CB,Olefsky JM,Reaven GM

    更新日期:1975-02-01 00:00:00

  • Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation.

    abstract::Insulin receptor substrate (IRS)-1 protein expression is markedly reduced in many insulin-resistant states, although the mechanism for this downregulation is unclear. In this study, we have investigated the early events in the insulin pathway that trigger the degradation of IRS-1. Incubation of the adipocytes with ins...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.1.24

    authors: Pederson TM,Kramer DL,Rondinone CM

    更新日期:2001-01-01 00:00:00

  • Insulin-potentiating action of a synthetic amino-terminal fragment of human growth hormone (hGH 1--15) in streptozotocin-diabetic rats.

    abstract::The hypoglycemic activity of the synthetic peptide fragment of human growth hormone, hGH 1--15, is insulin dependent, although it does not alter the circulating levels of plasma insulin in normal and diabetic rats. In severe diabetes induced by streptozotocin, the peptide had no effect on the basal levels of blood glu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.12.1126

    authors: Ng FM,Bornstein J

    更新日期:1979-12-01 00:00:00

  • Mode of onset of type 2 diabetes from normal or impaired glucose tolerance.

    abstract::Fasting plasma glucose concentrations (FPG) predict development of type 2 diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or as a step increase is not known. We measured plasma glucose and insulin levels during oral glucose testing in 35- to 64-year-old men and nonpregnant women from a p...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.1.160

    authors: Ferrannini E,Nannipieri M,Williams K,Gonzales C,Haffner SM,Stern MP

    更新日期:2004-01-01 00:00:00

  • Pancreatic β-cell failure mediated by mTORC1 hyperactivity and autophagic impairment.

    abstract::Hyperactivation of the mammalian target of rapamycin complex 1 (mTORC1) in β-cells is usually found as a consequence of increased metabolic load. Although it plays an essential role in β-cell compensatory mechanisms, mTORC1 negatively regulates autophagy. Using a mouse model with β-cell-specific deletion of Tsc2 (βTsc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0970

    authors: Bartolomé A,Kimura-Koyanagi M,Asahara S,Guillén C,Inoue H,Teruyama K,Shimizu S,Kanno A,García-Aguilar A,Koike M,Uchiyama Y,Benito M,Noda T,Kido Y

    更新日期:2014-09-01 00:00:00

  • Structure, function, and immunogenicity of human insulinoma cells.

    abstract::Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.9.1279

    authors: Thivolet CH,Demidem A,Haftek M,Durand A,Bertrand J

    更新日期:1988-09-01 00:00:00

  • Insulin resistance in obesity as analyzed by the response of glucose kinetics to glucagon infusion.

    abstract::A new approach has been developed to examine insulin sensitivity and resistance in vivo in man. In it, tracer methods are used, which permit the assessment of nonsteady state glucose kinetics by a method that is noninvasive and does not use pharmacologic agents. Graded doses of glucagon, infused intravenously, are use...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.3.169

    authors: Vranic M,Morita S,Steiner G

    更新日期:1980-03-01 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

  • Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

    abstract::The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein respon...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.46.12.2082

    authors: Dullaart RP,Hoogenberg K,Riemens SC,Groener JE,van Tol A,Sluiter WJ,Stulp BK

    更新日期:1997-12-01 00:00:00

  • Persistence of serum antibodies to 64,000-Mr islet cell protein after onset of type I diabetes.

    abstract::Antibodies to an islet protein of 64,000 Mr (64K antibodies) were measured in 15 diabetic children who were followed prospectively for up to 3 yr after onset of type I (insulin-dependent) diabetes. Of the 15 children, 12 were positive for 64K antibodies at diagnosis. Those patients who were negative for these antibodi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.39.6.653

    authors: Christie MR,Daneman D,Champagne P,Delovitch TL

    更新日期:1990-06-01 00:00:00

  • Clinical segmental pancreas transplantation without duct anastomosis in diabetic renal allograft recipients.

    abstract::Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.1.s10

    authors: Sutherland DE,Goetz FC,Najarian JS

    更新日期:1980-01-01 00:00:00

  • Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion.

    abstract::Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (thir...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.11.3196

    authors: Clegg DJ,Wortman MD,Benoit SC,McOsker CC,Seeley RJ

    更新日期:2002-11-01 00:00:00

  • Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.

    abstract:OBJECTIVE:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0705

    authors: Prieur X,Mok CY,Velagapudi VR,Núñez V,Fuentes L,Montaner D,Ishikawa K,Camacho A,Barbarroja N,O'Rahilly S,Sethi JK,Dopazo J,Orešič M,Ricote M,Vidal-Puig A

    更新日期:2011-03-01 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

  • Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion.

    abstract::Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (db) gene and is mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that the full-length leptin receptor (Ob-Rb), which is believed to transmit the l...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.2.313

    authors: Emilsson V,Liu YL,Cawthorne MA,Morton NM,Davenport M

    更新日期:1997-02-01 00:00:00

  • Hexosamine-induced fibronectin protein synthesis in mesangial cells is associated with increases in cAMP responsive element binding (CREB) phosphorylation and nuclear CREB: the involvement of protein kinases A and C.

    abstract::Hyperglycemia-induced alterations in mesangial (MES) cell function and extracellular matrix protein accumulation are seen in diabetic glomerulopathy. Recent studies have demonstrated that some of the effects of high glucose (HG) on cellular metabolism are mediated by the hexosamine biosynthesis pathway (HBP), in which...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.10.2355

    authors: Singh LP,Andy J,Anyamale V,Greene K,Alexander M,Crook ED

    更新日期:2001-10-01 00:00:00

  • Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells?

    abstract::Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic beta-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca2+ concentration) ...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.53.8.1942

    authors: Fridlyand LE,Philipson LH

    更新日期:2004-08-01 00:00:00