The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport
| Autor: | Thomas E. Jensen, Erik A. Richter, Nicoline R. Andersen, Ida L. Nielsen, Lykke Sylow, Lisbeth L. V. Møller, Jonas R. Knudsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Physiology medicine.medical_treatment Glucose uptake Skeletal muscle 030204 cardiovascular system & hematology lcsh:Physiology Signalling Pathways Mice 0302 clinical medicine Faculty of Science Insulin Glycolysis Original Research Mice Knockout Contraction lcsh:QP1-981 Chemistry p21‐activated kinase musculoskeletal system Cell biology medicine.anatomical_structure Models Animal Knockout mouse Female Endocrine and Metabolic Conditons Disorders and Treatments medicine.symptom tissues Muscle Contraction Signal Transduction Muscle contraction p21-activated kinase 03 medical and health sciences Physiology (medical) Metabolism and Regulation medicine Animals skeletal muscle Muscle Skeletal Soleus muscle Glucose transporter contraction Biological Transport glucose uptake Mice Inbred C57BL Glucose p21-Activated Kinases Muscle Contraction and Relaxation 030217 neurology & neurosurgery |
| Zdroj: | Møller, L L V, Nielsen, I L, Knudsen, J R, Andersen, N R, Jensen, T E, Sylow, L & Richter, E A 2020, ' The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport ', Physiological Reports, vol. 8, no. 12, e14460 . https://doi.org/10.14814/phy2.14460 Physiological Reports, Vol 8, Iss 12, Pp n/a-n/a (2020) Physiological Reports |
| DOI: | 10.14814/phy2.14460 |
| Popis: | Aim Muscle contraction stimulates skeletal muscle glucose transport. Since it occurs independently of insulin, it is an important alternative pathway to increase glucose transport in insulin‐resistant states, but the intracellular signaling mechanisms are not fully understood. Muscle contraction activates group I p21‐activated kinases (PAKs) in mouse and human skeletal muscle. PAK1 and PAK2 are downstream targets of Rac1, which is a key regulator of contraction‐stimulated glucose transport. Thus, PAK1 and PAK2 could be downstream effectors of Rac1 in contraction‐stimulated glucose transport. The current study aimed to test the hypothesis that PAK1 and/or PAK2 regulate contraction‐induced glucose transport. Methods Glucose transport was measured in isolated soleus and extensor digitorum longus (EDL) mouse skeletal muscle incubated either in the presence or absence of a pharmacological inhibitor (IPA‐3) of group I PAKs or originating from whole‐body PAK1 knockout, muscle‐specific PAK2 knockout or double whole‐body PAK1 and muscle‐specific PAK2 knockout mice. Results IPA‐3 attenuated (−22%) the increase in glucose transport in response to electrically stimulated contractions in soleus and EDL muscle. PAK1 was dispensable for contraction‐stimulated glucose transport in both soleus and EDL muscle. Lack of PAK2, either alone (−13%) or in combination with PAK1 (−14%), partly reduced contraction‐stimulated glucose transport compared to control littermates in EDL, but not soleus muscle. Conclusion Contraction‐stimulated glucose transport in isolated glycolytic mouse EDL muscle is partly dependent on PAK2, but not PAK1. In this study, we show that contraction‐stimulated glucose transport in isolated mouse skeletal muscle is unaffected by whole‐body knockout of PAK1. On the contrary, muscle‐specific knockout of PAK2 either alone or in combination with whole‐body PAK1 knockout partially reduces contraction‐stimulated glucose transport in glycolytic EDL muscle. These data suggest that contraction‐stimulated glucose transport in isolated glycolytic mouse EDL muscle is partly dependent on PAK2, but not PAK1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|