RETRACTED  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

doi:10.2337/db09-0979

RETRACTED 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 journal › Article › peer-review

66 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 language	English
Pages (from-to)	375-385
Number of pages	11
Journal	Diabetes
Volume	59
Issue number	2
DOIs	https://doi.org/10.2337/db09-0979
Publication status	Published - Feb 2010

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db09-0979

66 Citations
1 Article

RETRACTED . Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, and Harinder S. Hundal. Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. Diabetes 2010;59:375–385. DOI: 10.2337/db09-0979. PMID: 19933999. PMCID: PMC2809953
Lipina, C., Stretton, C., Hastings, S., Hundal, J. S., Mackie, K., Irving, A. & Hundal, H., Aug 2021, In: Diabetes. 70, 8, p. 1910 1 p., db21rt08a.
Research output: Contribution to journal › Article › peer-review

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@article{4e5ba96954ce43b7aa12f46cc095d5f9,

title = "RETRACTED 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",

keywords = "ENDOCANNABINOID SYSTEM, BETA-CELL, ANTAGONIST SR141716, INSULIN-RESISTANCE, ENERGY-BALANCE, CB1 ANTAGONISM, OBESITY, RIMONABANT, EXPRESSION, GLUCOSE",

author = "Christopher Lipina and Clare Stretton and Simon Hastings and Hundal, {Jonathan S.} and Ken Mackie and Irving, {Andrew J.} and Hundal, {Harinder S.}",

note = "Statement of Retraction. Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, and Harinder S. Hundal. Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. Diabetes 2010;59:375–385. DOI: 10.2337/db09-0979. PMID: 19933999. PMCID: PMC2809953 - June 17, 2021",

year = "2010",

month = feb,

doi = "10.2337/db09-0979",

language = "English",

volume = "59",

pages = "375--385",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "2",

}

TY - JOUR

T1 - RETRACTED 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.

N1 - Statement of Retraction. Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, and Harinder S. Hundal. Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. Diabetes 2010;59:375–385. DOI: 10.2337/db09-0979. PMID: 19933999. PMCID: PMC2809953 - June 17, 2021

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

SN - 0012-1797

VL - 59

SP - 375

EP - 385

JO - Diabetes

JF - Diabetes

IS - 2

ER -