Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells

Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, Harinder S. Hundal

    Research output: Contribution to journalArticle

    57 Citations (Scopus)

    Abstract

    OBJECTIVE-The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.

    RESEARCH DESIGN AND METHODS-Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.

    RESULTS-Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.

    CONCLUSIONS-Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism. Diabetes 59:375-385,2010

    Original languageEnglish
    Pages (from-to)375-385
    Number of pages11
    JournalDiabetes
    Volume59
    Issue number2
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • ENDOCANNABINOID SYSTEM
    • BETA-CELL
    • ANTAGONIST SR141716
    • INSULIN-RESISTANCE
    • ENERGY-BALANCE
    • CB1 ANTAGONISM
    • OBESITY
    • RIMONABANT
    • EXPRESSION
    • GLUCOSE

    Cite this

    Lipina, Christopher ; Stretton, Clare ; Hastings, Simon ; Hundal, Jonathan S. ; Mackie, Ken ; Irving, Andrew J. ; Hundal, Harinder S. / Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. In: Diabetes. 2010 ; Vol. 59, No. 2. pp. 375-385.
    @article{4e5ba96954ce43b7aa12f46cc095d5f9,
    title = "Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells",
    abstract = "OBJECTIVE-The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.RESEARCH DESIGN AND METHODS-Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.RESULTS-Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.CONCLUSIONS-Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism. Diabetes 59:375-385,2010",
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    author = "Christopher Lipina and Clare Stretton and Simon Hastings and Hundal, {Jonathan S.} and Ken Mackie and Irving, {Andrew J.} and Hundal, {Harinder S.}",
    year = "2010",
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    language = "English",
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    Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. / Lipina, Christopher; Stretton, Clare; Hastings, Simon; Hundal, Jonathan S.; Mackie, Ken; Irving, Andrew J.; Hundal, Harinder S.

    In: Diabetes, Vol. 59, No. 2, 02.2010, p. 375-385.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Regulation of MAP Kinase-Directed Mitogenic and Protein Kinase B-Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells

    AU - Lipina, Christopher

    AU - Stretton, Clare

    AU - Hastings, Simon

    AU - Hundal, Jonathan S.

    AU - Mackie, Ken

    AU - Irving, Andrew J.

    AU - Hundal, Harinder S.

    PY - 2010/2

    Y1 - 2010/2

    N2 - OBJECTIVE-The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.RESEARCH DESIGN AND METHODS-Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.RESULTS-Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.CONCLUSIONS-Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism. Diabetes 59:375-385,2010

    AB - OBJECTIVE-The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behavior and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic beta-cells, and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.RESEARCH DESIGN AND METHODS-Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists, and the resulting effects on insulin-regulated phosphatidylinositol 3 kinase (PI 3-kinase)-protein kinase B (PKB) and extracellular signal-related kinases 1/2 (ERK1/2)-directed signaling were determined.RESULTS-Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent mitogen-activated protein (MAP) kinase (ERK1/2) and the canonical PI 3-kinase/PKB signaling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regard to MAP kinase- and PKB-directed signaling.CONCLUSIONS-Our study provides evidence that signaling via cannabinoid receptors can significantly modulate mitogenic and metabolic signaling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism. Diabetes 59:375-385,2010

    KW - ENDOCANNABINOID SYSTEM

    KW - BETA-CELL

    KW - ANTAGONIST SR141716

    KW - INSULIN-RESISTANCE

    KW - ENERGY-BALANCE

    KW - CB1 ANTAGONISM

    KW - OBESITY

    KW - RIMONABANT

    KW - EXPRESSION

    KW - GLUCOSE

    U2 - 10.2337/db09-0979

    DO - 10.2337/db09-0979

    M3 - Article

    C2 - 19933999

    VL - 59

    SP - 375

    EP - 385

    JO - Diabetes

    JF - Diabetes

    SN - 0012-1797

    IS - 2

    ER -