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Título:
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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?
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Autor/a:
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López Cano, Carolina; Gutiérrez Carrasquilla, Liliana; Barbé Illa, Ferran; Sánchez Peña, Enric; Hernández García, Marta; Martí, Raquel; Ceperuelo-Mallafre, Vicky; Dalmases, Mireia; Fernández-Veledo, Sonia; Vendrell, Joan; Hernández, Cristina; Simó, Rafael; Lecube Torelló, Albert
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Notas:
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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.
This 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. |
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Materia(s):
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-Type 2 diabetes
-Hypoxia
-Metabolic control
-Chronodisruption
-Clock genes |
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Derechos:
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cc-by (c) López Cano, Carolina et al., 2020
http://creativecommons.org/licenses/by/4.0/
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Tipo de documento:
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Artículo
Artículo - Versión publicada |
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Editor:
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MDPI
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Compartir:
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