Monti Lucilla D, Setola Emanuela, Fragasso Gabriele, Camisasca Riccardo P, Lucotti Pietro, Galluccio Elena, Origgi Anna, Margonato Alberto, Piatti PierMarco
Laboratory L20, Core Lab., Diabetology, Endocrinology and Metabolic Disease Unit, IRCCS H San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E54-E59. doi: 10.1152/ajpendo.00083.2005. Epub 2005 Sep 20.
The aim of the present study was to evaluate the effect of prolonged inhibition of beta-oxidation on glucose and lipid muscle forearm metabolism and cGMP and endothelin-1 forearm release in patients with type 2 diabetes mellitus and ischemic cardiomyopathy. Fifteen patients were randomly allocated in a double-blind cross-over parallel study with trimetazidine (20 mg tid) or placebo lasting 15 days. At the end of each period, all patients underwent euglycemic hyperinsulinemic clamps with forearm indirect calorimetry and endothelial balance of vasodilator and vasoconstricor factors. Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompanied by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release. Forearm glucose oxidation significantly correlated with cGMP release (r=0.37, P<0.04), whereas forearm lipid oxidation positively correlated with endothelin-1 release (r=0.40, P<0.03). In conclusion, for the first time, we demonstrated that insulin-induced forearm glucose oxidation and forearm cGMP release were increased whereas forearm endothelin-1 release was decreased during trimetazidine treatment. Muscle's metabolic and vascular effects of trimetazidine add new interest in the use of trimetazidine in type 2 diabetic patients with cardiovascular disease.
本研究旨在评估长期抑制β-氧化对2型糖尿病和缺血性心肌病患者葡萄糖及脂质的前臂肌肉代谢以及环磷酸鸟苷（cGMP）和内皮素-1的前臂释放的影响。15例患者被随机分配至一项双盲交叉平行研究，分别接受曲美他嗪（20毫克，每日三次）或安慰剂治疗，为期15天。在每个阶段结束时，所有患者均接受正常血糖高胰岛素钳夹试验，并进行前臂间接测热法以及血管舒张因子和血管收缩因子的内皮平衡检测。与安慰剂相比，曲美他嗪可引起：1）胰岛素诱导的前臂葡萄糖摄取和葡萄糖氧化增加，同时前臂脂质氧化和柠檬酸释放减少；2）内皮素-1释放减少，同时前臂cGMP释放显著增加。前臂葡萄糖氧化与cGMP释放显著相关（r=0.37，P<0.04），而前臂脂质氧化与内皮素-1释放呈正相关（r=0.40，P<0.03）。总之，我们首次证明，在曲美他嗪治疗期间，胰岛素诱导的前臂葡萄糖氧化和前臂cGMP释放增加，而前臂内皮素-1释放减少。曲美他嗪对肌肉的代谢和血管作用为其在患有心血管疾病的2型糖尿病患者中的应用增添了新的关注点。
