RT Journal Article
T1 Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent
A1 Pérez García, Ana
A1 Hurtado Carneiro, Verónica
A1 Herrero de Dios, Carmen
A1 Dongil, Pilar
A1 García-Mauriño Múzquiz, José Enrique
A1 Sánchez De La Nieta García, María Dolores
A1 Sanz Miguel, María Del Carmen
A1 Álvarez García, Elvira
AB Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.
PB MDPI
SN 2072-6643
YR 2021
FD 2021-07-26
LK https://hdl.handle.net/20.500.14352/107709
UL https://hdl.handle.net/20.500.14352/107709
LA eng
NO Pérez-García, A.; Hurtado-Carneiro, V.; Herrero-De-Dios, C.; Dongil, P.; García-Mauriño, J.E.; Sánchez, M.D.; Sanz, C.; Álvarez, E. Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent. Nutrients 2021, 13, 2552. https://doi.org/10.3390/nu13082552
NO Ministerio de Economía, Industria y Competitividad (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 11 abr 2025