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dc.contributor.authorLópez Cano, Carolina
dc.contributor.authorGutiérrez Carrasquilla, Liliana
dc.contributor.authorBarbé Illa, Ferran
dc.contributor.authorSánchez Peña, Enric
dc.contributor.authorHernández García, Marta
dc.contributor.authorMartí, Raquel
dc.contributor.authorCeperuelo-Mallafre, Vicky
dc.contributor.authorDalmases, Mireia
dc.contributor.authorFernández-Veledo, Sonia
dc.contributor.authorVendrell, Joan
dc.contributor.authorHernández, Cristina
dc.contributor.authorSimó, Rafael
dc.contributor.authorLecube Torelló, Albert
dc.description.abstractLimited 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.ca_ES
dc.description.sponsorshipThis study was supported by grants from the Instituto de Salud Carlos III (PI 12/00803, PI 15/00260 and PI18/00964), Fondos FEDER “Una manera de hacer Europa”). CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and CIBER de Enfermedades Respiratorias (CIBERES) are initiatives of the Instituto Carlos III.ca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofJournal of Clinical Medicine, 2020, vol. 9, núm. 8, p. 2632ca_ES
dc.rightscc-by (c) López Cano, Carolina et al., 2020ca_ES
dc.subjectType 2 diabetesca_ES
dc.subjectMetabolic controlca_ES
dc.subjectClock genesca_ES
dc.titleEffect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?ca_ES

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cc-by (c) López Cano, Carolina et al., 2020
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