RESUMEN
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 pGSK3ß. 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.
RESUMEN
Durante los años de 1985 y 1986, se atendieron en el Hospital Infantil de México Federico Gómez, 5,777 niños menores de cinco años de edad con diarrea, de los cuales 729 (12,6%) se hospitalizaron; 429 del sexo masculino, 603 menores de unaño y 467 desnutridos. Las causas de ingreso más frecuentes fueron deshidratación grave (33.6%) y sospecha de septicemia (15.5%). Del total, fallecieron 83(11.4%), la mitad de ellos en las primeras 24 horas de hospitalización. Se observó correlación significativa entre la tasa de letalidad y el grado de desnutrición. Concluyó que es importante difundir el uso de la terapia de hidratación oral, como medida preventiva de deshidratación, a fin de disminuir la necesidad de hsopitalización y la tasa de letalidad por esta causa