title: AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle.
abstract: To examine the role of AMP-activated protein kinase (AMPK) in muscle glucose transport, we generated muscle-specific transgenic mice (TG) carrying cDNAs of inactive alpha2 (alpha2i TG) and alpha1 (alpha1i TG) catalytic subunits. Extensor digitorum longus (EDL) muscles from wild type and TG mice were isolated and subjected to a series of in vitro incubation experiments. In alpha2i TG mice basal alpha2 activity was barely detectable, whereas basal alpha1 activity was only partially reduced. Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK alpha2 activity in alpha2i TG mice, whereas alpha1 activation was attenuated by only 30-50%. Glucose transport was measured in vitro using isolated EDL muscles from alpha2i TG mice. AICAR- and rotenone-stimulated glucose transport was fully inhibited in alpha2i TG mice; however, the lack of AMPK alpha2 activity had no effect on contraction- or sorbitol-induced glucose transport. Similar to these observations in vitro, contraction-stimulated glucose transport, assessed in vivo by 2-deoxy-d-[(3)H]glucose incorporation into EDL, tibialis anterior, and gastrocnemius muscles, was normal in alpha2i TG mice. Thus, AMPK alpha2 activation is essential for some, but not all, insulin-independent glucose transport. Muscle contraction- and hyperosmolarity-induced glucose transport may be regulated by a redundant mechanism in which AMPK alpha2 is one of multiple signaling pathways.
authors.affiliation: Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Fujii
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Erin M
authors.initials: EM
authors.lastname: Kane
authors.forename: Richard C
authors.initials: RC
authors.lastname: Ho
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Peter
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Seifert
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
mesh_terms: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009994:Osmolar Concentration; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D015398:Signal Transduction; D013012:Sorbitol / Q000494:pharmacology
chemical_list: D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D012265:Ribonucleotides; D012402:Rotenone; D000620:Aminoimidazole Carboxamide; D013012:Sorbitol; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose