Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent
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...
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MDPI AG
2021-07-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/8/2552 |
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| author | Ana Pérez-García Verónica Hurtado-Carneiro Carmen Herrero-De-Dios Pilar Dongil José Enrique García-Mauriño María Dolores Sánchez Carmen Sanz Elvira Álvarez |
| author_facet | Ana Pérez-García Verónica Hurtado-Carneiro Carmen Herrero-De-Dios Pilar Dongil José Enrique García-Mauriño María Dolores Sánchez Carmen Sanz Elvira Álvarez |
| author_sort | Ana Pérez-García |
| collection | DOAJ |
| description | 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 <i>Pask</i> 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 <i>(Srebp1c)</i> 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 <i>(G6pase)</i> 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 <i>Pask</i> expression. |
| first_indexed | 2024-03-10T08:31:04Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T08:31:04Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-442ae9b80ac84cb7b980aff6fd555faf2023-11-22T09:02:26ZengMDPI AGNutrients2072-66432021-07-01138255210.3390/nu13082552Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK DependentAna Pérez-García0Verónica Hurtado-Carneiro1Carmen Herrero-De-Dios2Pilar Dongil3José Enrique García-Mauriño4María Dolores Sánchez5Carmen Sanz6Elvira Álvarez7Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Cell Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Cell Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Cell Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Cell Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, SpainGlucagon-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 <i>Pask</i> 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 <i>(Srebp1c)</i> 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 <i>(G6pase)</i> 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 <i>Pask</i> expression.https://www.mdpi.com/2072-6643/13/8/2552exendin-4glucosemetabolic sensorsdiabetesglucokinasefasting |
| spellingShingle | Ana Pérez-García Verónica Hurtado-Carneiro Carmen Herrero-De-Dios Pilar Dongil José Enrique García-Mauriño María Dolores Sánchez Carmen Sanz Elvira Álvarez Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent Nutrients exendin-4 glucose metabolic sensors diabetes glucokinase fasting |
| title | Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent |
| title_full | Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent |
| title_fullStr | Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent |
| title_full_unstemmed | Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent |
| title_short | Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent |
| title_sort | storage and utilization of glycogen by mouse liver during adaptation to nutritional changes are glp 1 and pask dependent |
| topic | exendin-4 glucose metabolic sensors diabetes glucokinase fasting |
| url | https://www.mdpi.com/2072-6643/13/8/2552 |
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