Washington University School of Medicine - Heart disease hits people with diabetes twice as often as people without diabetes.华盛顿大学医学院心脏病命中糖尿病人的两倍,这往往是患糖尿病的人. In those with diabetes, cardiovascular complications occur at an earlier age and often result in premature death, making heart disease the major killer of diabetic people.在那些患有糖尿病,心血管并发症发生在较早年龄往往造成过早死亡,使心脏病的主要杀手糖尿病人. But why is heart disease so prevalent among diabetics?但为什么是心脏病盛行糖尿病?

To help answer that question, researchers at Washington University School of Medicine in St. Louis have been analyzing the fat (lipid) composition of heart tissue from laboratory mice with diabetes.为了回答这个问题研究的华盛顿大学医学院,圣路易斯已分析脂肪(脂)组成的心脏组织,从实验鼠的糖尿病患者. The NIH-funded research has found that heart cells of diabetic mice lose an important lipid from cellular components that generate energy for the heart, and their latest research shows this happens at the very earliest stages of diabetes.国家卫生研究院资助的研究发现,心脏细胞,糖尿病小鼠失去一个重要脂类的细胞成分,产生能量的心脏,他们的最新研究显示,这种情况发生在很早期的糖尿病.

“Diabetic hearts run mostly on fats for fuel because glucose isn’t readily available to them,” says Richard Gross, M.D., Ph.D., director of the Division of Bioorganic Chemistry and Molecular Pharmacology and professor of medicine, of chemistry and of molecular biology and pharmacology. "糖尿病心而言,大部分脂肪油,因为葡萄糖是没有现成的,他们说: "理查德毛,医学博士,博士,科主任有机化学和分子药理学和医学教授,化学与分子生物学和药理学. “Unfortunately, this change in metabolism distorts the lipid composition of cell membranes causing abnormal physical properties and cellular dysfunction.” "不幸的是,这种变化在歪曲代谢脂质组成的细胞膜造成异常的物理性能和功能蜂窝"

The important lipid that the researchers found to be decreased in diabetes is cardiolipin.重要的脂质研究人员发现可减少糖尿病是心. “Cardiolipin” literally means heart fat, and the term was coined because cardiolipin was first discovered in beef hearts and is one of the most abundant lipids in heart tissue. "心" ,从字面上来看,即心脏病发和名词,因为心第一次被发现牛肉心中是一个最丰富的脂类心脏组织. This lipid has unusual physical properties that are essential for the operation of the energy-producing cell structures called mitochondria.这已血脂异常的物理性能,是必不可少的运作能量产生细胞结构称为线粒体.

When mitochondria lose a lot of their cardiolipin, they malfunction.当线粒体失去了很多他们的心,他们的故障. Their malfunction not only interferes with the energy supply of heart muscle cells, it also increases the amount of damaging oxygen-containing substances in the cells, creating unhealthy conditions that can lead to heart problems.其故障不仅干扰了能源供应的心脏肌肉细胞,而且也增加额损害氧含物质在细胞中,创造条件不佳,可导致心脏问题.

Interestingly, a rare genetic disorder — Barth syndrome — held a key to identifying cardiolipin decrease in diabetic hearts.有趣的是,豁嘴-巴特综合征举行的一个关键找出心减少糖尿病心. Children born with Barth syndrome have weak hearts and often die young from heart failure.患儿出生巴特综合征和心脏衰弱,常常英年早逝,从心脏衰竭. These children have mutations that prevent cells from producing enough cardiolipin.这些儿童有突变,防止细胞产生足够的心. The connection between cardiolipin and heart disease in Barth syndrome led the Washington University researchers to wonder if cardiolipin was also affected in diabetic hearts.连接心和心脏病巴特综合征率领华盛顿大学的研究人员想知道,如果是心,也影响了糖尿病的心.

But in order to measure cardiolipin, the researchers needed a way to distinguish it from the numerous other lipids found in heart cells.但为了衡量心,研究者需要一种方法来辨别它从众多其它脂类发现心脏细胞. Fortunately, Gross and his colleagues have been developing and refining a highly sophisticated set of techniques that allow them to separate and quantify thousands of different lipids based on their subtle structural differences.幸运的是,毛和他的同事们已制定并完善一个高度精密的一套技术,让他们分开,并量化数千种脂类基于其微妙的结构差异. The set of techniques has been termed “shotgun lipidomics” because they very rapidly determine which lipids are in tissues and blood.这套方法被称为"鸟枪lipidomics " ,因为他们很快确定其中类脂在组织和血液.

“Shotgun lipidomics provide a precise way to measure changes in heart lipid content,” says first author Xianlin Han, Ph.D., assistant professor of medicine. "鸟枪lipidomics提供一个确切的方法来测量变化心脏脂肪含量的变化,说: "第一作者仙林汉族,博士,助理医学教授. “We found a dramatic depletion of cardiolipin in heart muscle as early as five days after diabetes was induced in mice.” "我们发现了一个戏剧性的枯竭心在心脏肌肉早五天后诱发糖尿病老鼠"

“These results suggest that cardiolipin alterations underlie heart dysfunction in diabetic heart disease and may be a useful biomarker for diagnosing cardiovascular disease in diabetes,” Gross says. "这些结果表明,心改建理解心脏功能糖尿病及心脏病可能是一个有用的生物诊断心血管疾病,糖尿病, "毛说. “Measuring alterations may be a way to tell the severity of heart disease and to evaluate how well therapies work. "衡量改建可正步严重心脏病,并评估如何治疗工作. In addition, these findings suggest potential new therapeutic approaches.”此外,这些结果显示,潜在的新的治疗方法. "

Even though the research team found a depletion of an important type of lipid in diabetic heart tissue, diabetic heart muscle cells actually take in excess lipids.尽管研究小组发现了枯竭的一个重要类型血脂糖尿病心脏组织中,糖尿病人的心脏肌肉细胞中,实际上采取的过剩油脂. But as these lipids enter cells they activate lipid-digesting enzymes.但由于这些脂质进入细胞激活脂肪消化酵素. In previous studies, Gross and colleagues identified a particular lipid-digesting enzyme that becomes more active in diabetic heart muscle and contributes to the breakdown of cardiolipin.在先前的研究中,毛和他的同事发现了,尤其是脂肪消化酶变得更加活跃,糖尿病心脏肌肉,并有助于破裂的心.

Recently, Gross and his colleague David Mancuso, Ph.D., member of the division, found that mice engineered to produce too much of this enzyme in their hearts developed defects in mitochondrial function which became worse when they were fasted — a condition that, like diabetes, causes the heart to use lipids for fuel.近日,毛和他的同事大卫一气之下,博士委员,师发现,实验鼠设计生产了太多的这种酶在心中发达缺陷线粒体的功能,而成为坏时,被禁食一个条件,即像糖尿病,导致心用油脂为燃料. A 16-hour fast caused significant problems with the mouse hearts’ ability to pump blood, again implicating altered lipid metabolism, cardiolipin scarcity and mitochondrial impairment in heart disease using lipid as predominant fuel. 16小时快速造成重大问题与小鼠心脏的能力,血泵,再牵连改变脂质代谢,心稀缺和线粒体受损心脏病利用脂质作为主要燃料.

“The pieces of the puzzle of diabetic heart disease are now rapidly falling into place,” Gross says. "拼图糖尿病心脏病正迅速落入地方, "毛说. “By exploiting the novel technology of shotgun lipidomics, we have identified the increased activation of certain lipid-digesting enzymes and the decrease of cardiolipin as central aspects of this disorder. "利用新技术lipidomics猎枪后,我们发现有更多的活化某些脂类消化酶和减少心为中心,这方面障碍. We hope that these kinds of studies will enable physicians to diagnose diabetic cardiovascular disease sooner and treat it earlier.” [Han X, Yang J, Yang K, Zhao Z, Abendschein DR, Gross RW .我们希望这种研究将有助医生诊断糖尿病心血管疾病,并及早治疗. " [ ×汉,杨j号杨钾,赵z的阿本德沙因博士,毛万无一失. Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: a shotgun lipidomics study. Biochemistry 2007;46:6417-6428.]改建心肌心内容和组成发生在很早期糖尿病:鸟枪lipidomics研究. 2007 生物化学 ; 46:6417-6428 . ]

Gross adds that in addition to the effects on mitochondria, many of the membranes in heart cells, which are built from fatty molecules, are also adversely affected by the diabetic heart’s abnormal lipid metabolism.毛补充说,除了对线粒体,许多膜在心脏细胞,它是建立在从脂肪分子,也受到不利影响心脏病合并糖尿病的脂代谢异常. Furthermore, because fatty molecules are part of cells’ signaling mechanisms, numerous aspects of cellular physiology become altered.此外,由于脂肪分子部分的细胞信号传递机制的诸多方面蜂窝成为生理改变.