[WCIR2012]Humanin在衰老、糖尿病及动脉粥样硬化中的作用
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心脑血管  作者:P.Cohen 来源:未知 2013/1/14 14:50:00    加入收藏
内容概要:Humanin是日本学者新近发现的一种神经保护性多肽,能通过特异性地阻断某些细胞死亡的信号通路发挥抗细胞凋亡作用和神经保护机制,是较具前景的治疗阿尔茨海默病的药物。近来研究显示,其在衰老、糖尿病及动脉粥样硬化的发生发展过程中也发挥了重要的作用。

  ■ Pinchas Cohen    美国南加州大学
  International Diabetes: Recent studies have shown that the mitochondrial peptide, humanin, protects against Alzheimer’s disease and diabetes. Are those diverse protective effects interconnected or independent?
  Prof. Cohen: There is a link between Alzheimer’s disease and type 2 diabetes, and it is likely that there is a common mechanism for the development of the two diseases. Therefore it is not entirely surprising that interventions that help one would also affect the other disease. However, the exact mechanism is still not entirely elucidated. The general inflammatory state and the metabolic status which are both normalized by the presence of endogenous humanin, as well as exogenous humanin, may play an important role in it. We also have evidence that higher humanin levels are associated with a lesser likelihood of having diseases such as atherosclerosis in addition to Alzheimer’s and diabetes.
  International Diabetes: You mentioned that the general mechanism for the protective effect is not yet well known, but focusing solely on insulin regulation, do you have any ideas as to how humanin protects against diabetes?
  Prof. Cohen: Diabetes has several elements of influence on pathways of glucose regulation. Humanin acts in two major ways. Humanin acts on the brain in the hypothalamus through a unique receptor called the humanin receptor, which is composed of the subunits of the CNTF receptor, the IL27 receptor, and another component called the gp130. This unique humanin receptor in the hypothalamus signals through a pathway known as STAT3 phosphorylation, which then leads to a rapid nuclear event and ends up with a signal from the hypothalamus to the liver through the vagus nerve. This hypothalamic-hepatic signal tells the liver to decrease hepatic glucose production. That is the central mechanism by which humanin acts as an insulin sensitizer. In addition, we are seeing that humanin also helps with both the production of insulin and insulin action.
  International Diabetes: It has been described that there is an epidemic of diabetes worldwide that is predicted to grow. How does the increasing elderly population fit into the statistics of the diabetes epidemic worldwide compared to the general population?
  Prof. Cohen: The population in general is aging, and aging more rapidly in Asia than elsewhere. In fact, in the United States, about 15% of the population is over 65 and predicted to grow to about 25% by 2050. In China, only about 10% is over 65 right now but it is predicted to grow to 35% by 2050 due to expected increases in longevity and the presence of the one child policy. The "silver tsunami" of an increased elderly population will increase the incidence of Alzheimer’s disease and diabetes. There is a lot of discussion about the increasing rate of diabetes in young people, but the rate of increase in older people is much more dramatic. It has always been known that the frequency of diabetes rises with age and the frequency of diabetes at any particular age has not changed dramatically, except for the fact that there are a lot more older people around every year, which explains the rise in numbers.
  《国际糖尿病》:近期研究提示,线粒体多肽humanin对阿尔茨海默病及糖尿病均具有保护效应。其上述效应是相互关联还是独立起效?
  Cohen教授:阿尔茨海默病与2型糖尿病是相互关联的,它们可能存在共同的发病机制。因此,针对其中一种疾病的干预措施会对另一种疾病产生影响也就不足为奇。目前,两者相关联的具体机制尚不完全清楚,全身炎症性反应或代谢状态可能在其中发挥了一定的作用。humanin则能使上述情况恢复正常。有证据显示,较高的humanin与较低的动脉粥样硬化、阿尔茨海默病及糖尿病等疾病风险具有相关性。
  《国际糖尿病》:Humanin发挥保护作用的机制尚未阐明,目前主要聚焦在胰岛素调节方面。在您看来,humanin是如何对糖尿病患者发挥保护作用的?
  Cohen教授:糖尿病可通过几种不同的途径来影响血糖调节,humanin可作用于其中的两条主要途径。其通过作用于下丘脑的humanin受体(由CNTF受体、IL27受体和gp130 组成),促使STAT3磷酸化从而导致快速核转位继而使信号从下丘脑通过迷走神经传输至肝脏,最终减少肝糖生成。以上是humanin作为胰岛素增敏剂的核心机制。此外,我们发现,humanin还可促进胰岛素的生成并能增强胰岛素的作用。
  《国际糖尿病》:您的研究是否发现了可使人体内humanin水平自然升高的方法?
  Cohen教授:目前已确定humanin水平的高低存在遗传倾向性,双亲与子女的humanin水平具有相关性。迄今为止,还未发现饮食干预对人体humanin水平有显著影响。我们仍在试图阐释是否有药物或补充剂可影响humanin的水平。
  《国际糖尿病》:与一般人群相比,日益扩大的老年人群如何增加全球糖尿病发病的统计量?
  Cohen教授:全球均面临着老龄化,尤以亚洲老龄化速度最快。目前,美国65岁以上老年人约占15%,预计到2050年将达到25%;中国目前65岁以上老年人所占比例仅有10%,但2050年则预计会增加至35%。这主要是源于寿命延长以及“一孩”计划生育政策。我们形象地将老龄化称之为“银色海啸”,其必将导致阿尔茨海默病及糖尿病发病增加。人们对年轻人群糖尿病发病率的增加进行了很多的讨论,但实际上老年人糖尿病的发病率增幅更大。众所周知,糖尿病发病率会随年龄的增长而增加。但特定年龄段的糖尿病发病率并没有显著的变化,老年人口的逐年增加才是其增长的原因所在。
 

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