RT Journal Article
T1 Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy
A1 Hurtado Carneiro, Verónica
A1 Le Baut Ayuso, Yannick
A1 Velázquez, Esther
A1 Flores Lamas, Cinthya
A1 Fernández de La Rosa, Rubén
A1 García García, Luis
A1 Gómez Oliver, Francisca
A1 Ruiz Albusac, Juan Miguel
A1 Pozo García, Miguel Ángel
AB Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3β. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.
PB Cell Press
SN 2405-8440
YR 2024
FD 2024-08-15
LK https://hdl.handle.net/20.500.14352/110078
UL https://hdl.handle.net/20.500.14352/110078
LA eng
NO Hurtado-Carneiro, V., LeBaut-Ayuso, Y., Velázquez, E., Flores-Lamas, C., Fernández-de la Rosa, R., García-García, L., Gómez-Oliver, F., Ruiz-Albusac, J. M., & Pozo, M. Á. (2024). Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy. Heliyon, 10(15), e35752. https://doi.org/10.1016/j.heliyon.2024.e35752
NO Fundación Ramón Areces
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 10 abr 2025