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国际糖尿病 >>EASD年会
[EASD2011]第五届Albert Renold奖获得者Marc Prentki专访:肿瘤与糖尿病关系及如何干预胰岛细胞凋亡
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专家访谈 综合领域 作者:M.Prentki 来源:国际糖尿病 2011/9/16 15:14:00    加入收藏
内容概要:《国际糖尿病》:以往的一些研究显示,二甲双胍可以降低糖尿病患者的癌症发生风险,但一些专家认为这个结果只是由于研究设计而导致的错觉。请问您是怎么认为的?

    Marc  Prentki  加拿大蒙特利尔大学
    <International Diabetes>: Some previous studies have shown that metformin could reduce the risk of cancers in diabetic patients, however some experts think that that result is just an illusion due to research design.  What is your opinion about that?

   《国际糖尿病》:以往的一些研究显示,二甲双胍可以降低糖尿病患者的癌症发生风险,但一些专家认为这个结果只是由于研究设计而导致的错觉。请问您是怎么认为的?
 
    Prof. Prentki: Actually I am very interested in this.  I believe metformin can do this because of the work I am currently doing with metformin.  Metformin is thought, as far as diabetes is concerned, to work mainly through changes in hepatic glucose production.  However, it is a drug less known for its influence at the mitochondrial level in all cell types because of its ability to influence the mitochondrial electron transport chain.  Metformin is believed to have this effect in the electron transport chain not only in liver cells but in all cells of the body.  As for cancer this is very interesting because metformin may be able to influence what we have since called “metabolic deceleration.”  By slowing down metabolism glucose and fatty acids are oxidized less or oxidized more slowly at a given concentration of the fuel.  We have shown that in tumor beta cells that the addition of metformin to these cells there is an inhibition of growth and glucose metabolism is decelerated.  Basically, if you examine the dose dependence of glucose metabolism it is shifted to the right.  At the same concentration of glucose you metabolize less and to have the same metabolism glucose consumption must increase.  Why is this interesting?  Because it has been realized that cancer is not only a disease of defects in gene expression or mutation but also a metabolic disease in that cells need nutrients to grow.  If you have more nutrients like glucose or fat then the cancer cells would have resources to grow.  If there existed a drug that reduces metabolism of glucose in all tissue at a given concentration in the blood then this would have an inhibitory effect on cancer.  The reduction of metabolism means cancer has less fuel to grow.  The concept of deceleration whereby you slow down metabolism has a positive effect, not only in diabetes but also on the inhibition of cancer.  

    Prentki教授: 事实上,我对这个问题非常感兴趣。因为我目前正对二甲双胍进行研究,我相信二甲双胍具有这种作用。在治疗糖尿病方面,人们认为二甲双胍作用的主要机制是改变肝糖原的产生。由于二甲双胍可以影响细胞线粒体内的电子传递链,因此也可能在线粒体水平对机体内的各种细胞均产生影响,目前人们对这方面还知之甚少。二甲双胍对电子传递链的作用不仅仅局限于肝细胞,而是对机体内的各种细胞均具有作用。对于癌症来说,这个现象非常有意义,因为二甲双胍可能对我们所说的“代谢减速”过程产生影响。二甲双胍通过减慢代谢速率,使葡萄糖和脂肪酸的氧化量减少,使氧化速率比葡萄糖和脂肪酸浓度相同而不用二甲双胍时减慢。我们的研究结果显示,在肿瘤性的beta细胞中加入二甲双胍后,肿瘤细胞的生长受到了抑制,血糖代谢出现了减速。此时检查葡萄糖剂量依赖性的葡萄糖代谢率会发现已经基本上恢复了正常。服用二甲双胍以后,在相同的血糖浓度条件下,血糖代谢会降低;此时想要代谢和不服药时相同量的血糖,就必须要增加摄入的血糖量。为什么说这个研究结果很有意义呢?因为人们已经认识到,癌症不仅仅是因一种基因表达或变异缺陷而导致的疾病,同时也似一种代谢性疾病,因为肿瘤细胞的生长需要营养物质。葡萄糖和脂肪这样的营养物质越多,肿瘤细胞生长所需的物质来源就越多。如果存在某种药物能够在血液中葡萄糖浓度固定的条件下降低机体所有组织中的葡萄糖代谢率,就能够同时癌症产生抑制作用。代谢减速(代谢速率降低)机制不仅对糖尿病的治疗有效,对于抑制肿瘤也有效果。



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