Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?
López-Cano, Carolina (Institut de Recerca Biomèdica de Lleida)
Gutiérrez-Carrasquilla, Liliana (Institut de Recerca Biomèdica de Lleida)
Barbé, Ferran (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Sánchez, Enric (Institut de Recerca Biomèdica de Lleida)
Hernández, Marta (Institut de Recerca Biomèdica de Lleida)
Martí, Raquel (Institut de Recerca Biomèdica de Lleida)
Ceperuelo Mallafré, Victòria (Hospital Universitari Joan XXIII de Tarragona)
Dalmases, Mireia (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Fernández-Veledo, Sonia (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Vendrell, Joan (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Hernández, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Simó Canonge, Rafael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lecube, Albert (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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-1α (HIF-1α) and HIF-2α 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-1α 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-1α and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1α and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1α. Type 2 diabetes modifies the expression of HIF-1α and clock genes, which correlates with the degree of metabolic control.
Ajuts:	Ministerio de Economía y Competitividad PI 12/00803 Ministerio de Economía y Competitividad PI 15/00260 Instituto de Salud Carlos III PI18/00964
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Type 2 diabetes ; Hypoxia ; Metabolic control ; Chronodisruption ; Clock genes
Publicat a:	Journal of clinical medicine, Vol. 9 (august 2020) , ISSN 2077-0383

DOI: 10.3390/jcm9082632
PMID: 32823749

10 p, 1.3 MB

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