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Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373481" target="_blank" >RIV/00216208:11130/17:10373481 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00064203:_____/17:10373481

  • Výsledek na webu

    <a href="https://doi.org/10.1515/jpem-2017-0163" target="_blank" >https://doi.org/10.1515/jpem-2017-0163</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1515/jpem-2017-0163" target="_blank" >10.1515/jpem-2017-0163</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

  • Popis výsledku v původním jazyce

    Background: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the K-ATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic beta-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to beta-cell dysfunction presenting as CHI. Methods: As a model, we used a patient with transient CHI that paternally inherited novel heterozygous mutations in ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp) genes. The pathogenic effects on the pancreatic beta-cells function were examined in an in vitro functional study using radioactive rubidium efflux assay. Results: We showed that the activation of the mutated K-ATP channels by diazoxide was decreased by 60.9% in the channels with the heterozygous combination of both mutations compared to the wild type channels. This could indicate the pathogenic effect on the pancreatic beta-cell function leading to CHI although conclusive evidence is needed to be added. Conclusions: Our findings may widen the spectrum of genetic causes of CHI and suggest a novel pathogenic mechanism of CHI that must however, be further investigated.

  • Název v anglickém jazyce

    Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

  • Popis výsledku anglicky

    Background: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the K-ATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic beta-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to beta-cell dysfunction presenting as CHI. Methods: As a model, we used a patient with transient CHI that paternally inherited novel heterozygous mutations in ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp) genes. The pathogenic effects on the pancreatic beta-cells function were examined in an in vitro functional study using radioactive rubidium efflux assay. Results: We showed that the activation of the mutated K-ATP channels by diazoxide was decreased by 60.9% in the channels with the heterozygous combination of both mutations compared to the wild type channels. This could indicate the pathogenic effect on the pancreatic beta-cell function leading to CHI although conclusive evidence is needed to be added. Conclusions: Our findings may widen the spectrum of genetic causes of CHI and suggest a novel pathogenic mechanism of CHI that must however, be further investigated.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30202 - Endocrinology and metabolism (including diabetes, hormones)

Návaznosti výsledku

  • Projekt

  • Návaznosti

    S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Journal of Pediatric Endocrinology &amp; Metabolism

  • ISSN

    0334-018X

  • e-ISSN

  • Svazek periodika

    30

  • Číslo periodika v rámci svazku

    12

  • Stát vydavatele periodika

    DE - Spolková republika Německo

  • Počet stran výsledku

    5

  • Strana od-do

    1311-1315

  • Kód UT WoS článku

    000416610500013

  • EID výsledku v databázi Scopus

    2-s2.0-85037078545