Hagve 2015 Am J Physiol Endocrinol Metab

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Hagve M, Gjessing PF, Fuskevåg OM, Larsen TS, Irtun Ø (2015) Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance. Am J Physiol Endocrinol Metab 308:E613-20.

» PMID: 25670828 Open access

Hagve M, Gjessing PF, Fuskevag OM, Larsen TS, Irtun Oe (2015) Am J Physiol Endocrinol Metab

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.

Keywords: Reactive oxygen species, Surgery, Insulin resistance, mitochondria; Skeletal muscle, Liver, Amplex Red

O2k-Network Lab: NO Tromsoe Larsen TS


Labels: MiParea: Respiration  Pathology: Diabetes  Stress:Oxidative stress;RONS  Organism: Pig  Tissue;cell: Skeletal muscle, Liver  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k