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• W2912269718 abstract "Glucose transport into skeletal muscle is essential for maintaining whole-body glucose homeostasis and accounts for the majority of glucose disposal in response to insulin. The group I p21-activated kinase (PAK) isoforms PAK1 and PAK2 are in skeletal muscle activated in response to insulin and evidence suggests that PAK1 is necessary for insulin-stimulated GLUT4 translocation. In accordance, insulin-induced PAK1 and PAK2 signalling are impaired in insulin-resistant skeletal muscle. However, the role of PAK1 and PAK2 in insulin-stimulated glucose uptake in mature skeletal muscle has not been determined. The aim of the present investigation was to determine the requirement for PAK1 and PAK2 in whole-body glucose homeostasis and insulin-stimulated glucose uptake in skeletal muscle. Therefore, glucose uptake was measured in isolated skeletal muscle incubated with a pharmacological inhibitor (IPA-3) of group I PAKs and in muscle from whole-body PAK1 knockout (KO), muscle-specific PAK2 (m)KO and double whole-body PAK1 and muscle-specific PAK2 knockout mice. Whole-body respiratory exchange ratio, indicative of substrate utilization, was largely unaffected by lack of PAK1 and/or PAK2. Whole-body glucose tolerance was mildly impaired in PAK2 mKO, but not PAK1 KO mice. In contrast to a previous study of GLUT4 translocation in PAK1 KO mice, PAK1 KO muscles displayed normal insulin-stimulated glucose uptake in vivo and in isolated muscle. On the contrary, glucose uptake was slightly reduced in response to insulin in glycolytic extensor digitorum longus muscle lacking PAK2. In conclusion, the current study demonstrates that group I PAKs are largely dispensable for the regulation of whole-body glucose homeostasis and skeletal muscle glucose uptake. Thus, the present study challenges that group I PAKs, and especially PAK1, are necessary regulators of insulin-stimulated glucose uptake in skeletal muscle" @default.
• W2912269718 created "2019-02-21" @default.
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• W2912269718 date "2019-11-15" @default.
• W2912269718 modified "2023-09-23" @default.
• W2912269718 title "Group I p21-activated kinases (PAKs) are largely dispensable for insulin-stimulated glucose uptake in mouse skeletal muscle" @default.
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