Role of AMP--activated protein kinase in the control of glucose homeostasis.
Skeletal muscle insulin resistance is a hallmark feature of Type 2 diabetes. Physical exercise/muscle contraction elicits an insulin-independent increase in glucose transport and perturbation of this pathway may bypass defective insulin signaling. To date, the exercise-responsive signaling molecules governing glucose metabolism in skeletal muscle are largely unknown. AMP-activated protein kinase (AMPK) has been suggested as one of the exercise-responsive signaling molecules involved in glucose homeostasis and consequently it has been heavily explored as a pharmacological target for the treatment of Type 2 diabetes. AMPK exists in heterotrimeric complexes composed of a catalytic alpha-subunit and regulatory beta- and gamma-subunits. The gamma3-isoform of AMPK is expressed specifically in skeletal muscle of humans and rodents and this tissue specific expression pattern offers selectivity in AMPK action. Furthermore, mutations in the AMPK gamma3-isoform may provide protection from diet-induced insulin resistance by increasing lipid oxidation in the presence of increased lipid supply. This review highlights the current understanding of the role of the regulatory AMPK gamma3-isoform in the control of skeletal muscle metabolism.
Barnes
B R
BR
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Zierath
J R
JR
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001692:Biological Transport; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015444:Exercise; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D010805:Physical Conditioning, Animal; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
D007328:Insulin; D009097:Multienzyme Complexes; D020033:Protein Isoforms; C526225:PRKAG3 protein, human; C526221:Prkag3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose