Articles producció científica> Bioquímica i Biotecnologia

Decreased expression of hepatic glucokinase in type 2 diabetes

  • Identification data

    Identifier: imarina:9293243
    Authors:
    Haeusler, Rebecca A.Camastra, StefaniaAstiarraga, BrennoNannipieri, MonicaAnselmino, MarcoFerrannini, Ele
    Abstract:
    Background/objectives: Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK).Methods: We examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0.Results: In diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2.Conclusion: These findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population. (C) 2014 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Others:

    Author, as appears in the article.: Haeusler, Rebecca A.; Camastra, Stefania; Astiarraga, Brenno; Nannipieri, Monica; Anselmino, Marco; Ferrannini, Ele;
    Department: Bioquímica i Biotecnologia
    URV's Author/s: Domínguez Porfirio, Brenno
    Keywords: Postprandial hyperglycemia Metabolism Liver Humans Glucose-production Gluconeogenesis Glucokinase Gene-expression Foxo1 Fatty rats Fasting hyperglycemia Diabetes De-novo lipogenesis
    Abstract: Background/objectives: Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK).Methods: We examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0.Results: In diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2.Conclusion: These findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population. (C) 2014 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
    Thematic Areas: Molecular biology Endocrinology & metabolism Ciências biológicas ii Cell biology
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: brenno.dominguez@urv.cat
    Author identifier: 0000-0003-2216-8974
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.sciencedirect.com/science/article/pii/S2212877814002087?via%3Dihub
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Molecular Metabolism. 4 (3): 222-226
    APA: Haeusler, Rebecca A.; Camastra, Stefania; Astiarraga, Brenno; Nannipieri, Monica; Anselmino, Marco; Ferrannini, Ele; (2015). Decreased expression of hepatic glucokinase in type 2 diabetes. Molecular Metabolism, 4(3), 222-226. DOI: 10.1016/j.molmet.2014.12.007
    Article's DOI: 10.1016/j.molmet.2014.12.007
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2015
    Publication Type: Journal Publications
  • Keywords:

    Cell Biology,Endocrinology & Metabolism,Molecular Biology
    Postprandial hyperglycemia
    Metabolism
    Liver
    Humans
    Glucose-production
    Gluconeogenesis
    Glucokinase
    Gene-expression
    Foxo1
    Fatty rats
    Fasting hyperglycemia
    Diabetes
    De-novo lipogenesis
    Molecular biology
    Endocrinology & metabolism
    Ciências biológicas ii
    Cell biology
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