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Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells

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Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells. / Turban, Sophie; Stretton, Clare; Drouin, Olivier; Green, Charlotte J.; Watson, Maria L.; Gray, Alexander; Ross, Fiona; Lantier, Louise; Viollet, Benoit; Hardie, D.Grahame; Marette, Andre; Hundal, Harinder S. (Lead / Corresponding author).

In: Journal of Biological Chemistry, Vol. 287, No. 24, 08.06.2012, p. 20088-20099.

Research output: Contribution to journalArticle

Harvard

Turban, S, Stretton, C, Drouin, O, Green, CJ, Watson, ML, Gray, A, Ross, F, Lantier, L, Viollet, B, Hardie, DG, Marette, A & Hundal, HS 2012, 'Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells' Journal of Biological Chemistry, vol 287, no. 24, pp. 20088-20099., 10.1074/jbc.M111.330746

APA

Turban, S., Stretton, C., Drouin, O., Green, C. J., Watson, M. L., Gray, A., ... Hundal, H. S. (2012). Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells. Journal of Biological Chemistry, 287(24), 20088-20099. 10.1074/jbc.M111.330746

Vancouver

Turban S, Stretton C, Drouin O, Green CJ, Watson ML, Gray A et al. Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells. Journal of Biological Chemistry. 2012 Jun 8;287(24):20088-20099. Available from: 10.1074/jbc.M111.330746

Author

Turban, Sophie; Stretton, Clare; Drouin, Olivier; Green, Charlotte J.; Watson, Maria L.; Gray, Alexander; Ross, Fiona; Lantier, Louise; Viollet, Benoit; Hardie, D.Grahame; Marette, Andre; Hundal, Harinder S. (Lead / Corresponding author) / Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells.

In: Journal of Biological Chemistry, Vol. 287, No. 24, 08.06.2012, p. 20088-20099.

Research output: Contribution to journalArticle

Bibtex - Download

@article{f251022beed0430d92eed1d454125f6a,
title = "Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells",
author = "Sophie Turban and Clare Stretton and Olivier Drouin and Green, {Charlotte J.} and Watson, {Maria L.} and Alexander Gray and Fiona Ross and Louise Lantier and Benoit Viollet and D.Grahame Hardie and Andre Marette and Hundal, {Harinder S.}",
year = "2012",
doi = "10.1074/jbc.M111.330746",
volume = "287",
number = "24",
pages = "20088--20099",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells

A1 - Turban,Sophie

A1 - Stretton,Clare

A1 - Drouin,Olivier

A1 - Green,Charlotte J.

A1 - Watson,Maria L.

A1 - Gray,Alexander

A1 - Ross,Fiona

A1 - Lantier,Louise

A1 - Viollet,Benoit

A1 - Hardie,D.Grahame

A1 - Marette,Andre

A1 - Hundal,Harinder S.

AU - Turban,Sophie

AU - Stretton,Clare

AU - Drouin,Olivier

AU - Green,Charlotte J.

AU - Watson,Maria L.

AU - Gray,Alexander

AU - Ross,Fiona

AU - Lantier,Louise

AU - Viollet,Benoit

AU - Hardie,D.Grahame

AU - Marette,Andre

AU - Hundal,Harinder S.

PY - 2012/6/8

Y1 - 2012/6/8

N2 - The importance of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) as effectors of metformin (Met) action on glucose uptake (GU) in skeletal muscle cells was investigated. GUin L6 myotubes was stimulated 2-fold following 16 h of Met treatment and acutely enhanced by insulin in an additive fashion. Insulin-stimulatedGUwas sensitive to PI3K inhibition, whereas that induced by Met was not. Met and its related biguanide, phenformin, stimulated AMPK activation/phosphorylation to a level comparable with that induced by the AMPK activator, 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). However, the increase in GU elicited by AICAR was significantly lower than that induced by either biguanide. Expression of a constitutively active AMPK mimicked the effects of AICAR on GU, whereas a dominant interferingAMPK or shRNA silencing of AMPK prevented AICAR-stimulated GU and Met-induced AMPK signaling but only repressed biguanide- stimulated GU by ~20%. Consistent with this, analysis of GU in muscle cells from a1 /a2 AMPK-deficient mice revealed a significant retention of Met-stimulated GU, being reduced by ~35% compared with that of wild type cells. Atypical PKCs (aPKCs) have been implicated in Met-stimulated GU, and in line with this, Met and phenformin induced activation/phosphorylation of aPKC in L6 myotubes. However, although cellular depletion of aPKC (>90%) led to loss in biguanide-induced aPKC phosphorylation, it had no effect on Met-stimulated GU, whereas inhibitors targeting novel/conventional PKCs caused a significant reduction in biguanide-induced GU. Our findings indicate that although Met activates AMPK, a significant component of Met-stimulated GU in muscle cells is mediated via an AMPK-independent mechanism that involves novel/conventional PKCs. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

AB - The importance of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) as effectors of metformin (Met) action on glucose uptake (GU) in skeletal muscle cells was investigated. GUin L6 myotubes was stimulated 2-fold following 16 h of Met treatment and acutely enhanced by insulin in an additive fashion. Insulin-stimulatedGUwas sensitive to PI3K inhibition, whereas that induced by Met was not. Met and its related biguanide, phenformin, stimulated AMPK activation/phosphorylation to a level comparable with that induced by the AMPK activator, 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). However, the increase in GU elicited by AICAR was significantly lower than that induced by either biguanide. Expression of a constitutively active AMPK mimicked the effects of AICAR on GU, whereas a dominant interferingAMPK or shRNA silencing of AMPK prevented AICAR-stimulated GU and Met-induced AMPK signaling but only repressed biguanide- stimulated GU by ~20%. Consistent with this, analysis of GU in muscle cells from a1 /a2 AMPK-deficient mice revealed a significant retention of Met-stimulated GU, being reduced by ~35% compared with that of wild type cells. Atypical PKCs (aPKCs) have been implicated in Met-stimulated GU, and in line with this, Met and phenformin induced activation/phosphorylation of aPKC in L6 myotubes. However, although cellular depletion of aPKC (>90%) led to loss in biguanide-induced aPKC phosphorylation, it had no effect on Met-stimulated GU, whereas inhibitors targeting novel/conventional PKCs caused a significant reduction in biguanide-induced GU. Our findings indicate that although Met activates AMPK, a significant component of Met-stimulated GU in muscle cells is mediated via an AMPK-independent mechanism that involves novel/conventional PKCs. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

UR - http://www.scopus.com/inward/record.url?scp=84862001123&partnerID=8YFLogxK

U2 - 10.1074/jbc.M111.330746

DO - 10.1074/jbc.M111.330746

M1 - Article

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 24

VL - 287

SP - 20088

EP - 20099

ER -

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