RT Journal Article
T1 PAS Kinase deficiency alters the glucokinase function and hepatic metabolism
A1 Pérez García, Ana
A1 Dongil, Pilar
A1 Hurtado Carneiro, Verónica
A1 Blázquez Fernández, Enrique
A1 Sanz Miguel, María Del Carmen
A1 Álvarez García, Elvira
AB The liver controls metabolic homeostasis in response to fasting and refeeding periods. Glucokinase (GCK) adjusts hepatic glucose phosphorylation to blood glucose levels, acting as a glucose sensor. Our objective was to determine whether PAS kinase (PASK), a nutrient sensor, could be affecting the expression or activity of liver GCK and the response to fasting and refeeding states of key hepatic metabolic pathways. PASK-deficient mice have impaired insulin signaling (AKT overactivation). Furthermore, PASK deficiency modified the expression of several transcription factors involved in the adjustment to fasting and refeeding. Foxo1 decreased under fasting conditions, while Ppara and Pparg were overexpressed in PASK-deficient mice. However, PEPCK protein levels were similar or higher, while the expression of Cpt1a decreased in PASK-deficient mice. By contrast, Lxra and Chrebp were overexpressed after refeeding, while the expression of Acc and Fas decreased in PASK-deficient mice. Likewise, with a decreased expression of Gck and increased nuclear location of the complex GCK-GCKR, GCK activity decreased in PASK-deficient mice. Therefore, PASK regulated some of the genes and proteins responsible for glucose sensing, such as glucokinase, and for insulin signalling, affecting glucose and lipid metabolism and consequently certain critical hepatic functions.
PB Springer Nature
SN 2045-2322
YR 2018
FD 2018-07-23
LK https://hdl.handle.net/20.500.14352/107733
UL https://hdl.handle.net/20.500.14352/107733
LA eng
NO Pérez-García A, Dongil P, Hurtado-Carneiro V, Blazquez E, Sanz C, Alvarez E. PAS Kinase deficiency alters the glucokinase function and hepatic metabolism. Sci Rep. 2018 Jul 23;8(1):11091. doi: 10.1038/s41598-018-29234-8. PMID: 30038292; PMCID: PMC6056484.
NO Universidad Complutense-Programa de Financiación Banco Santander para la Creación y Consolidación de Equipos de Investigación [GR3/14]Fondos FEDER
NO Universidad Complutense de Madrid
NO Banco Santander
NO European Commission
NO Fundación Mutua Madrileña
NO Instituto de Salud Carlos III
NO Ministerio de Economía, Comercio y Empresa (España)
DS Docta Complutense
RD 20 abr 2025