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;
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.
Am J Physiol Endocrinol Metab. 2015 Apr 15;308(8):E613-20. doi: 10.1152/ajpendo.00459.2014. Epub 2015 Feb 10.
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.
术后急性胰岛素抵抗的发展是一个负面因素，但其中的机制尚不完全清楚。我们研究了腹部大手术后第 2 天猪骨骼肌和肝脏中胰岛素敏感性、线粒体功能、酶活性和活性氧（ROS）释放的术后变化。通过 D-[6,6-²H₂]葡萄糖输注和高胰岛素正葡萄糖钳夹评估外周和肝胰岛素敏感性。手术创伤引起外周胰岛素敏感性下降（约 34%，P<0.01），而肝胰岛素敏感性保持不变。从骨骼肌中分离出的肌内纤维（IFM）和肌小节下的线粒体（SSM）显示，ADP 刺激的丙酮酸呼吸（V(ADP)）术后下降（分别约 61%，P<0.05 和约 40%，P<0.001），而谷氨酸和棕榈酰-L-肉碱（PC）的 V(ADP)则不变。SSM 中 PC 的线粒体漏呼吸增加（1.9 倍，P<0.05）和 IFM 中增加（2.5 倍，P<0.05），表明 FFA 诱导的解偶联。丙酮酸脱氢酶复合物（PDC）的活性降低（约 32%，P<0.01），与外周胰岛素敏感性的下降呈正相关（r=0.748，P<0.05）。其他所有线粒体酶的活性均不变。在肝脏中未观察到线粒体功能的变化。通过分光荧光法测量线粒体 H₂O₂和 O₂·⁻的排放，SSM、IFM 和肝线粒体中的 H₂O₂增加（分别约为 2.3、2.5 和 2.3 倍，均 P<0.05）。我们的结论是，术后阶段骨骼肌线粒体 PDC 活性和丙酮酸氧化能力的损害伴随着 ROS 释放的增加，提示线粒体功能与急性术后胰岛素抵抗的发展之间存在联系。
