title: AMPKα2 deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle.
abstract: AMP-activated protein kinase (AMPK) is a fuel sensor in skeletal muscle with multiple downstream signaling targets that may be triggered by increases in intracellular Ca(2+) concentration ([Ca(2+)]). The purpose of this study was to determine whether increases in intracellular [Ca(2+)] induced by caffeine act solely via AMPKα(2) and whether AMPKα(2) is essential to increase glucose uptake, fatty acid (FA) uptake, and FA oxidation in contracting skeletal muscle. Hindlimbs from wild-type (WT) or AMPKα(2) dominant-negative (DN) transgene mice were perfused during rest (n = 11), treatment with 3 mM caffeine (n = 10), or muscle contraction (n = 11). Time-dependent effects on glucose and FA uptake were uncovered throughout the 20-min muscle contraction perfusion period (P < 0.05). Glucose uptake rates did not increase in DN mice during muscle contraction until the last 5 min of the protocol (P < 0.05). FA uptake rates were elevated at the onset of muscle contraction and diminished by the end of the protocol in DN mice (P < 0.05). FA oxidation rates were abolished in the DN mice during muscle contraction (P < 0.05). The DN transgene had no effect on caffeine-induced FA uptake and oxidation (P > 0.05). Glucose uptake rates were blunted in caffeine-treated DN mice (P < 0.05). The DN transgene resulted in a greater use of intramuscular triglycerides as a fuel source during muscle contraction. The DN transgene did not alter caffeine- or contraction-mediated changes in the phosphorylation of Ca(2+)/calmodulin-dependent protein kinase I or ERK1/2 (P > 0.05). These data suggest that AMPKα(2) is involved in the regulation of substrate uptake in a time-dependent manner in contracting muscle but is not necessary for regulation of FA uptake and oxidation during caffeine treatment.
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0652, USA.
authors.forename: Marcia J
authors.initials: MJ
authors.lastname: Abbott
authors.forename: Lindsey D
authors.initials: LD
authors.lastname: Bogachus
authors.forename: Lorraine P
authors.initials: LP
authors.lastname: Turcotte
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism*; D010477:Perfusion; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D019308:Palmitic Acid; D002110:Caffeine; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose