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Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
Am J Physiol Endocrinol Metab. 2004 Aug; 287(2):E310-7.AJ

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.

Authors+Show Affiliations

MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Scotland, UK. k.sakamoto@dundee.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15068958

Citation

Sakamoto, Kei, et al. "Activity of LKB1 and AMPK-related Kinases in Skeletal Muscle: Effects of Contraction, Phenformin, and AICAR." American Journal of Physiology. Endocrinology and Metabolism, vol. 287, no. 2, 2004, pp. E310-7.
Sakamoto K, Göransson O, Hardie DG, et al. Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. Am J Physiol Endocrinol Metab. 2004;287(2):E310-7.
Sakamoto, K., Göransson, O., Hardie, D. G., & Alessi, D. R. (2004). Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. American Journal of Physiology. Endocrinology and Metabolism, 287(2), E310-7.
Sakamoto K, et al. Activity of LKB1 and AMPK-related Kinases in Skeletal Muscle: Effects of Contraction, Phenformin, and AICAR. Am J Physiol Endocrinol Metab. 2004;287(2):E310-7. PubMed PMID: 15068958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. AU - Sakamoto,Kei, AU - Göransson,Olga, AU - Hardie,D Grahame, AU - Alessi,Dario R, Y1 - 2004/04/06/ PY - 2004/4/8/pubmed PY - 2004/8/31/medline PY - 2004/4/8/entrez SP - E310 EP - 7 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 287 IS - 2 N2 - 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/15068958/Activity_of_LKB1_and_AMPK_related_kinases_in_skeletal_muscle:_effects_of_contraction_phenformin_and_AICAR_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00074.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -