Changes in Exercise-Induced Gene Expression in 5′-AMP–Activated Protein Kinase γ3–Null and γ3 R225Q Transgenic Mice
| Autor: | Dana Galuska, Brian R. Barnes, Yun Chau Long, Tatiana L. Steiler, Ying Leng, Leif Andersson, Juleen R. Zierath, Jørgen F. P. Wojtaszewski |
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| Rok vydání: | 2005 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Endocrinology Diabetes and Metabolism Transgene Mice Transgenic AMP-Activated Protein Kinases Mice AMP-activated protein kinase Lipid oxidation Physical Conditioning Animal Internal medicine Internal Medicine medicine Animals Humans Insulin Muscle Skeletal Glycogen synthase Protein kinase A Swimming Triglycerides Mice Knockout biology Glucose transporter Skeletal muscle Glucose medicine.anatomical_structure Endocrinology Amino Acid Substitution biology.protein Protein Kinases GLUT4 |
| Zdroj: | Diabetes. 54:3484-3489 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.54.12.3484 |
| Popis: | 5′-AMP–activated protein kinase (AMPK) is important for metabolic sensing. We used AMPKγ3 mutant–overexpressing Tg-Prkag3 225Q and AMPKγ3-knockout Prkag3 −/− mice to determine the role of the AMPKγ3 isoform in exercise-induced metabolic and gene regulatory responses in skeletal muscle. Mice were studied after 2 h swimming or 2.5 h recovery. Exercise increased basal and insulin-stimulated glucose transport, with similar responses among genotypes. In Tg-Prkag3 225Q mice, acetyl-CoA carboxylase (ACC) phosphorylation was increased and triglyceride content was reduced after exercise, suggesting that this mutation promotes greater reliance on lipid oxidation. In contrast, ACC phosphorylation and triglyceride content was similar between wild-type and Prkag3 −/− mice. Expression of genes involved in lipid and glucose metabolism was altered by genetic modification of AMPKγ3. Expression of lipoprotein lipase 1, carnitine palmitoyl transferase 1b, and 3-hydroxyacyl–CoA dehydrogenase was increased in Tg-Prkag3 225Q mice, with opposing effects in Prkag3 −/− mice after exercise. GLUT4, hexokinase II (HKII), and glycogen synthase mRNA expression was increased in Tg-Prkag3 225Q mice after exercise. GLUT4 and HKII mRNA expression was increased in wild-type mice and blunted in Prkag3 −/− mice after recovery. In conclusion, the Prkag3 225Q mutation, rather than presence of a functional AMPKγ3 isoform, directly promotes metabolic and gene regulatory responses along lipid oxidative pathways in skeletal muscle after endurance exercise. |
| Databáze: | OpenAIRE |
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