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bioRxiv · 10.1101/2020.01.29.925024

The role of group I p21-activated kinases in contraction-stimulated skeletal muscle glucose transport

Moller, L. L. V.·Nielsen, I. L.·Knudsen, J. R.·Andersen, N. R.·Jensen, T. E.·Sylow, L.·Richter, E. A.
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Abstract

AimMuscle contraction stimulates skeletal muscle glucose transport. Since it occurs independently of insulin, it is an important alternative pathway to increase glucose uptake in insulin-resistant states, but the intracellular signalling 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. MethodsGlucose 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 (KO), muscle-specific PAK2 (m)KO or double whole-body PAK1 and muscle-specific PAK2 knockout mice. ResultsIPA-3 attenuated (-22%) the increase in muscle glucose transport in response to electrically-stimulated contraction. PAK1 was dispensable for contraction-stimulated glucose uptake in both soleus and EDL muscle. Lack of PAK2, either alone (-13%) or in combination with PAK1 (-14%), reduced contraction-stimulated glucose transport compared to control littermates in EDL, but not soleus muscle. ConclusionContraction-stimulated glucose transport in isolated glycolytic mouse EDL muscle is partly dependent on PAK2, but not PAK1.

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Moller, L. L. V., Nielsen, I. L., Knudsen, J. R., Andersen, N. R., Jensen, T. E., Sylow, L., Richter, E. A.. 2020-01-30. The role of group I p21-activated kinases in contraction-stimulated skeletal muscle glucose transport. https://doi.org/10.1101/2020.01.29.925024

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