title: Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance.
abstract: Development of acute insulin resistance represents a negative factor after surgery, but the underlying mechanisms are not fully understood. We investigated the postoperative changes in insulin sensitivity, mitochondrial function, enzyme activities, and release of reactive oxygen species (ROS) in skeletal muscle and liver in pigs on the 2nd postoperative day after major abdominal surgery. Peripheral and hepatic insulin sensitivity were assessed by D-[6,6-²H₂]glucose infusion and hyperinsulinemic euglycemic step clamping. Surgical trauma elicited a decline in peripheral insulin sensitivity (∼34%, P<0.01), whereas hepatic insulin sensitivity remained unchanged. Intramyofibrillar (IFM) and subsarcolemma mitochondria (SSM) isolated from skeletal muscle showed a postoperative decline in ADP-stimulated respiration (V(ADP)) for pyruvate (∼61%, P<0.05, and ∼40%, P<0.001, respectively), whereas V(ADP) for glutamate and palmitoyl-L-carnitine (PC) was unchanged. Mitochondrial leak respiration with PC was increased in SSM (1.9-fold, P<0.05) and IFM (2.5-fold, P<0.05), indicating FFA-induced uncoupling. The activity of the pyruvate dehydrogenase complex (PDC) was reduced (∼32%, P<0.01) and positively correlated to the decline in peripheral insulin sensitivity (r=0.748, P<0.05). All other mitochondrial enzyme activities were unchanged. No changes in mitochondrial function in liver were observed. Mitochondrial H₂O₂ and O₂·⁻ emission was measured spectrofluorometrically, and H₂O₂ was increased in SSM, IFM, and liver mitochondria (∼2.3-, ∼2.5-, and ∼2.3-fold, respectively, all P<0.05). We conclude that an impairment in skeletal muscle mitochondrial PDC activity and pyruvate oxidation capacity arises in the postoperative phase along with increased ROS emission, suggesting a link between mitochondrial function and development of acute postoperative insulin resistance.
authors: Laboratory of Surgical Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; martin.hagve@uit.no.
authors: Martin
authors: M
authors: Hagve
authors: Laboratory of Surgical Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Digestive Surgery, University Hospital of North Norway, Tromsø, Norway; and.
authors: Petter Fosse
authors: PF
authors: Gjessing
authors: Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway, Tromsø, Norway.
authors: Ole Martin
authors: OM
authors: Fuskevåg
authors: Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway;
authors: Terje S
authors: TS
authors: Larsen
authors: Laboratory of Surgical Research, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Digestive Surgery, University Hospital of North Norway, Tromsø, Norway; and.
authors: Øivind
authors: Ø
authors: Irtun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003433:Crosses, Genetic; D015309:Glucose Clamp Technique; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009210:Myofibrils / Q000201:enzymology / Q000378:metabolism; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D011183:Postoperative Complications / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D015415:Biomarkers; D011768:Pyruvate Dehydrogenase Complex; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid
keywords: insulin resistance; liver; mitochondria; reactive oxygen species; skeletal muscle; surgery