Cited by 299Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismMuscle Physiology and Disorders

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Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR

Sakamoto, Kei, Göransson, Olga, Hardie, D. Grahame, Alessi, Dario R.·2004·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00074.2004

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Abstract

Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes. We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have also reported that LKB1 activates 11 other AMPK-related kinases. The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes. In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle. Contraction in situ, induced via sciatic nerve stimulation, significantly increased AMPKalpha2 activity and phosphorylation in multiple muscle fiber types without affecting LKB1 activity. Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity. Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle. The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1. They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.

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Authors: Sakamoto, K., Göransson, O., Hardie, D. G., & Alessi, D. R.
Affiliations: University of Dundee (GB)
ORCID: Sakamoto, Kei
Göransson, Olga
Hardie, D. Grahame
Alessi, Dario R.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2004-08
Volume: 287
Issue: 2
Pages: E310-E317
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00074.2004
OpenAlex: W2050427373
Cited by: 299
References: 32
Citations by year: 2025: 6 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 13 · 2015: 13 · 2014: 24 · 2013: 14 · 2012: 20
FWCI: 10.06
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
Lund University Publications (Lund University) (submittedVersion)
Funders: University of Bristol
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: LKB1, AMPK, AMPK-related kinases, skeletal muscle, muscle contraction, phenformin, AICAR, AMPKα1, AMPKα2, MARK kinases, physical activity, type 2 diabetes, muscle fiber type, sciatic nerve stimulation
MeSH terms: AMP-Activated Protein Kinase Kinases, Aminoimidazole Carboxamide, Animals, Cells, Cultured, Enzyme Activation, Fibroblasts, HeLa Cells, Humans, Hypoglycemic Agents, Isoenzymes, Male, Multienzyme Complexes, Muscle Contraction, Organ Culture Techniques, Phenformin, Physical Conditioning, Animal, Ribonucleotides, Rats, Wistar, Protein Serine-Threonine Kinases, Mice, Knockout, Muscle, Skeletal, Mice, Rats, AMP-Activated Protein Kinases

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Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR

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