The p21-activated kinase 2 (PAK2), but not PAK1, regulates contraction-stimulated skeletal muscle glucose transport

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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.

OriginalsprogEngelsk
Artikelnummere14460
TidsskriftPhysiological Reports
Vol/bind8
Udgave nummer12
Antal sider13
ISSN2051-817X
DOI
StatusUdgivet - 2020

Bibliografisk note

CURIS 2020 NEXS 211 (Open Access --> upload pdf-fil)

ID: 244042875