Cree Melanie G, Zwetsloot Jennifer J, Herndon David N, Newcomer Bradley R, Fram Ricki Y, Angel Carlos, Green Justin M, Dohm Gerald L, Sun Dayoung, Aarsland Asle, Wolfe Robert R
Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas, USA.
J Burn Care Res. 2008 Jul-Aug;29(4):585-94. doi: 10.1097/BCR.0b013e31817db88f.
Impaired fatty acid oxidation occurs with type 2 diabetes and is associated with accumulations of intracellular lipids, which may increase diacylglycerol (DAG), stimulate protein kinase C activity, and inactivate insulin signaling. Glucose and fat metabolism are altered in burn patients, but have never been related to intracellular lipids or insulin signaling. Thirty children sustaining >40% total body surface area burns were studied acutely with glucose and palmitate tracer infusions and a hyper-insulinemic euglycemic clamp. Muscle triglyceride, DAG, fatty acyl CoA, and insulin signaling were measured. Liver and muscle triglyceride levels were measured with magnetic resonance spectroscopy. Muscle samples from healthy children were controls for DAG concentrations. Insulin sensitivity was reduced and correlated with whole body palmitate beta-oxidation (P = .004). Muscle insulin signaling was not stimulated by hyper-insulinemia. Tissue triglyceride concentrations and activated protein kinase C-beta were elevated, whereas the concentration of DAG was similar to the controls. Free fatty acid profiles of muscle triglyceride did not match DAG. Insulin resistance following burn injury is accompanied by decreased insulin signaling and increased protein kinase C-beta activation. The best metabolic predictor of insulin resistance in burned patients was palmitate oxidation.
2型糖尿病患者会出现脂肪酸氧化受损，这与细胞内脂质蓄积有关，细胞内脂质蓄积可能会增加二酰甘油（DAG）、刺激蛋白激酶C活性并使胰岛素信号失活。烧伤患者的葡萄糖和脂肪代谢会发生改变，但从未与细胞内脂质或胰岛素信号相关联。对30名全身表面积烧伤超过40%的儿童进行了急性研究，通过输注葡萄糖和棕榈酸示踪剂以及进行高胰岛素正常血糖钳夹试验。测量了肌肉甘油三酯、DAG、脂肪酰辅酶A和胰岛素信号。用磁共振波谱法测量肝脏和肌肉甘油三酯水平。将健康儿童的肌肉样本作为DAG浓度的对照。胰岛素敏感性降低，且与全身棕榈酸β氧化相关（P = 0.004）。高胰岛素血症并未刺激肌肉胰岛素信号。组织甘油三酯浓度和活化的蛋白激酶C-β升高，而DAG浓度与对照组相似。肌肉甘油三酯的游离脂肪酸谱与DAG不匹配。烧伤后胰岛素抵抗伴随着胰岛素信号减少和蛋白激酶C-β活化增加。烧伤患者胰岛素抵抗的最佳代谢预测指标是棕榈酸氧化。
