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Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?

  • Datos identificativos

    Identificador: imarina:7810770
    Autores:
    López-Cano C, Gutiérrez-Carrasquilla L, Barbé F, Sánchez E, Hernández M, Martí R, Ceperuelo-Mallafre V, Dalmases M, Fernández-Veledo S, Vendrell J, Hernández C, Simó R, Lecube A
    Resumen:
    Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) and HIF-2 alpha relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 +/- 688.2 vs. 1730.4 +/- 694.4 uM/L,p= 0.013) and pyruvate (61.9 +/- 25.6 vs. 50.3 +/- 23.1 uM/L,p= 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1 alpha expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU),p <= 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes' expression. Univariate analysis showed that HIF-1 alpha and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1 alpha and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1 alpha. Type 2 diabetes modifies the expression of HIF-1 alpha and clock genes, which correlates with the degree of metabolic control.
  • Otros:

    Autor según el artículo: López-Cano C, Gutiérrez-Carrasquilla L, Barbé F, Sánchez E, Hernández M, Martí R, Ceperuelo-Mallafre V, Dalmases M, Fernández-Veledo S, Vendrell J, Hernández C, Simó R, Lecube A
    Departamento: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    Autor/es de la URV: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
    Palabras clave: Type 2 diabetes Sleep Rhythms Night Metabolic control Hypoxia Endocrine Clock genes Circadian clock Chronodisruption Cellular adaptation Apnea
    Resumen: Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) and HIF-2 alpha relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 +/- 688.2 vs. 1730.4 +/- 694.4 uM/L,p= 0.013) and pyruvate (61.9 +/- 25.6 vs. 50.3 +/- 23.1 uM/L,p= 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1 alpha expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU),p <= 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes' expression. Univariate analysis showed that HIF-1 alpha and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1 alpha and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1 alpha. Type 2 diabetes modifies the expression of HIF-1 alpha and clock genes, which correlates with the degree of metabolic control.
    Áreas temáticas: Medicine, general & internal Medicine (miscellaneous) Medicine (all)
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
    Identificador del autor: 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115
    Fecha de alta del registro: 2024-09-07
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://www.mdpi.com/2077-0383/9/8/2632
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Journal Of Clinical Medicine. 9 (8): 1-10
    Referencia de l'ítem segons les normes APA: López-Cano C, Gutiérrez-Carrasquilla L, Barbé F, Sánchez E, Hernández M, Martí R, Ceperuelo-Mallafre V, Dalmases M, Fernández-Veledo S, Vendrell J, He (2020). Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?. Journal Of Clinical Medicine, 9(8), 1-10. DOI: 10.3390/jcm9082632
    DOI del artículo: 10.3390/jcm9082632
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2020
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Medicine (Miscellaneous),Medicine, General & Internal
    Type 2 diabetes
    Sleep
    Rhythms
    Night
    Metabolic control
    Hypoxia
    Endocrine
    Clock genes
    Circadian clock
    Chronodisruption
    Cellular adaptation
    Apnea
    Medicine, general & internal
    Medicine (miscellaneous)
    Medicine (all)
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