title: Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle.
abstract: The signaling mechanisms that mediate the important effects of contraction to increase glucose transport in skeletal muscle are not well understood, but are known to occur through an insulin-independent mechanism. Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport. This finding, in conjunction with previous studies of ablated AMPKalpha2 activity showing no effect on contraction-stimulated glucose transport, suggests that one or more AMPK-related protein kinases are important for this process. Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice. Expression of a mutant SNARK in mouse tibialis anterior muscle impaired contraction-stimulated, but not insulin-stimulated, glucose transport. Whole-body SNARK heterozygotic knockout mice also had impaired contraction-stimulated glucose transport in skeletal muscle, and knockdown of SNARK in C2C12 muscle cells impaired sorbitol-stimulated glucose transport. SNARK is activated by muscle contraction and is a unique mediator of contraction-stimulated glucose transport in skeletal muscle.
authors: Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
authors: Ho-Jin
authors: HJ
authors: Koh
authors: Taro
authors: T
authors: Toyoda
authors: Nobuharu
authors: N
authors: Fujii
authors: Michelle M
authors: MM
authors: Jung
authors: Amee
authors: A
authors: Rathod
authors: R Jan-Willem
authors: RJ
authors: Middelbeek
authors: Sarah J
authors: SJ
authors: Lessard
authors: Jonas T
authors: JT
authors: Treebak
authors: Katsuya
authors: K
authors: Tsuchihara
authors: Hiroyasu
authors: H
authors: Esumi
authors: Erik A
authors: EA
authors: Richter
authors: Jørgen F P
authors: JF
authors: Wojtaszewski
authors: Michael F
authors: MF
authors: Hirshman
authors: Laurie J
authors: LJ
authors: Goodyear
mesh_terms: D055372:AMP-Activated Protein Kinases; D000328:Adult; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation; D015444:Exercise / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013012:Sorbitol / Q000494:pharmacology
chemical_list: D007328:Insulin; D013012:Sorbitol; C486061:NUAK2 protein, human; D017346:Protein Serine-Threonine Kinases; C553187:SNARK protein, mouse; C491654:Stk11 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose