The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
| Autor: | Sebastian Beck Jørgensen, Emmanuel Gomas, Claudia Lenzner, Axel Kahn, Benoit Viollet, Morris J. Birnbaum, Christophe Perrin, Erik A. Richter, Alain Géloën, Daisy Flamez, Gaël Nicolas, Fabrizio Andreelli, Rémy Burcelin, David Carling, Sophie Vaulont, James Mu, Olivier Baud, Myriam Bennoun, Frans Schuit, Jørgen F. P. Wojtaszewski |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Time Factors Genotype medicine.medical_treatment AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Article Mice AMP-activated protein kinase Multienzyme Complexes Internal medicine Catalytic Domain medicine Animals Insulin Glycogen synthase Muscle Skeletal Alleles Mice Knockout Glucose tolerance test biology medicine.diagnostic_test Dose-Response Relationship Drug Muscles Body Weight Glucose transporter AMPK Biological Transport General Medicine Glucose Tolerance Test Insulin oscillation Protein Structure Tertiary Mice Inbred C57BL Insulin receptor Blotting Southern Endocrinology Glucose Liver biology.protein Glycogen |
| Popis: | AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity. |
| Databáze: | OpenAIRE |
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