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1 MRC Protein Phosphorylation Unit, University of Dundee, Dundee, United Kingdom
2 Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
* To whom correspondence should be addressed. E-mail: k.sakamoto{at}dundee.ac.uk.
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
analogue phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide
riboside (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 AMPKrelated
kinase activity in rat skeletal muscle. Contraction in situ, induced via sciatic nerve
stimulation, significantly increased AMPK
2 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 AMPK1
and AMPK2, 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 activate AMPK by a mechanism which 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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E. B. Taylor, D. Hurst, L. J. Greenwood, J. D. Lamb, T. D. Cline, S. N. Sudweeks, and W. W. Winder Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1082 - E1089. [Abstract] [Full Text] [PDF]
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