Han X, Abendschein D R, Kelley J G, Gross R W
Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8020, St. Louis, MO 63110, USA.
Biochem J. 2000 Nov 15;352 Pt 1(Pt 1):79-89.
Intrinsic cardiac dysfunction during the diabetic state has been causally linked to changes in myocardial lipid metabolism. However, the precise alterations in the molecular species of myocardial polar and non-polar lipids during the diabetic state and their responses to insulin have not been investigated. Herein we demonstrate four specific alterations in rat myocardial lipid molecular species after induction of the diabetic state by streptozotocin treatment: (i) a massive remodelling of triacylglycerol molecular species including a >5-fold increase in tripalmitin mass and a 60% decrease in polyunsaturated triacylglycerol molecular species mass (i.e. triacylglycerols containing at least one acyl residue with more than two double bonds); (ii) a 46% increase in myocardial phosphatidylinositol mass; (iii) a 44% increase in myocardial plasmenylethanolamine mass and (iv) a 22% decrease in 1-stearoyl-2-arachidonoyl phosphatidylethanolamine content. Each of the changes in phospholipid classes, subclasses and individual molecular species were prevented by insulin treatment after induction of the diabetic state. In sharp contrast, the alterations in triacylglycerol molecular species were not preventable by peripheral insulin treatment after induction of the diabetic state. These results segregate diabetes-induced alterations in myocardial lipid metabolism into changes that can be remedied or not by routine peripheral insulin treatment and suggest that peripheral insulin therapy alone may not be sufficient to correct all of the metabolic alterations present in diabetic myocardium.
糖尿病状态下的心脏内在功能障碍与心肌脂质代谢变化存在因果关系。然而，糖尿病状态下心肌极性和非极性脂质分子种类的具体改变及其对胰岛素的反应尚未得到研究。在此，我们证明了链脲佐菌素诱导糖尿病状态后大鼠心肌脂质分子种类的四种特定改变：（i）三酰甘油分子种类的大量重塑，包括三棕榈精质量增加超过5倍，多不饱和三酰甘油分子种类质量减少60%（即含有至少一个具有两个以上双键的酰基残基的三酰甘油）；（ii）心肌磷脂酰肌醇质量增加46%；（iii）心肌缩醛磷脂酰乙醇胺质量增加44%；（iv）1-硬脂酰-2-花生四烯酰磷脂酰乙醇胺含量减少22%。糖尿病状态诱导后，胰岛素治疗可防止磷脂类、亚类和单个分子种类的每一项变化。与之形成鲜明对比的是，糖尿病状态诱导后，外周胰岛素治疗无法防止三酰甘油分子种类的改变。这些结果将糖尿病诱导的心肌脂质代谢改变分为可通过常规外周胰岛素治疗纠正或不可纠正的变化，并表明仅外周胰岛素治疗可能不足以纠正糖尿病心肌中存在的所有代谢改变。
