Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content

L Al-Khalili, A V Chibalin, K Kannisto, B B Zhang, J Permert, G D Holman, E Ehrenborg, V D H Ding, J R Zierath, A Krook

Research output: Contribution to journalArticle

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Abstract

In mature human skeletal muscle, insulin-stimulated glucose transport is mediated primarily via the GLUT4 glucose transporter. However, in contrast to mature skeletal muscle, cultured muscle expresses significant levels of the GLUT1 glucose transporter. To assess the relative contribution of these two glucose transporters, we used a novel photolabelling techniques to assess the cell surface abundance of GLUT1 and GLUT4 specifically in primary cultures of human skeletal muscle. We demonstrate that insulin-stimulated glucose transport in cultured human skeletal muscle is mediated by GLUT4, as no effect on GLUT1 appearance at the plasma membrane was noted. Furthermore, GLUT4 mRNA and protein increased twofold (p < 0.05), after differentiation, whereas GLUT1 mRNA and protein decreased 55% (p < 0.005). Incubation of differentiated human skeletal muscle cells with a non-peptide insulin mimetic significantly (p < 0.05) increased glucose uptake and glycogen synthesis. Thus, cultured myotubes are a useful tool to facilitate biological and molecular validation of novel pharmacological agents aimed to improve glucose metabolism in skeletal muscle.
Original languageEnglish
Pages (from-to)991-998
Number of pages8
JournalCellular and Molecular Life Sciences (CMLS)
Volume60
Issue number5
DOIs
Publication statusPublished - 2003

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Muscle Cells
Cell Differentiation
Skeletal Muscle
Insulin
Facilitative Glucose Transport Proteins
Glucose
Glucose Transporter Type 1
Glucose Transporter Type 4
Messenger RNA
Skeletal Muscle Fibers
Glycogen
Cell Membrane
Pharmacology
Muscles

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Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content. / Al-Khalili, L; Chibalin, A V; Kannisto, K; Zhang, B B; Permert, J; Holman, G D; Ehrenborg, E; Ding, V D H; Zierath, J R; Krook, A.

In: Cellular and Molecular Life Sciences (CMLS), Vol. 60, No. 5, 2003, p. 991-998.

Research output: Contribution to journalArticle

Al-Khalili, L, Chibalin, AV, Kannisto, K, Zhang, BB, Permert, J, Holman, GD, Ehrenborg, E, Ding, VDH, Zierath, JR & Krook, A 2003, 'Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content', Cellular and Molecular Life Sciences (CMLS), vol. 60, no. 5, pp. 991-998. https://doi.org/10.1007/s00018-003-3001-3
Al-Khalili, L ; Chibalin, A V ; Kannisto, K ; Zhang, B B ; Permert, J ; Holman, G D ; Ehrenborg, E ; Ding, V D H ; Zierath, J R ; Krook, A. / Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content. In: Cellular and Molecular Life Sciences (CMLS). 2003 ; Vol. 60, No. 5. pp. 991-998.
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AU - Permert, J

AU - Holman, G D

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AU - Krook, A

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AB - In mature human skeletal muscle, insulin-stimulated glucose transport is mediated primarily via the GLUT4 glucose transporter. However, in contrast to mature skeletal muscle, cultured muscle expresses significant levels of the GLUT1 glucose transporter. To assess the relative contribution of these two glucose transporters, we used a novel photolabelling techniques to assess the cell surface abundance of GLUT1 and GLUT4 specifically in primary cultures of human skeletal muscle. We demonstrate that insulin-stimulated glucose transport in cultured human skeletal muscle is mediated by GLUT4, as no effect on GLUT1 appearance at the plasma membrane was noted. Furthermore, GLUT4 mRNA and protein increased twofold (p < 0.05), after differentiation, whereas GLUT1 mRNA and protein decreased 55% (p < 0.005). Incubation of differentiated human skeletal muscle cells with a non-peptide insulin mimetic significantly (p < 0.05) increased glucose uptake and glycogen synthesis. Thus, cultured myotubes are a useful tool to facilitate biological and molecular validation of novel pharmacological agents aimed to improve glucose metabolism in skeletal muscle.

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