博客与个人生活—一篇JBC文章

坚持博客下去不是件容易的事情,如果总是脱离生活,自己的生活,博客的生命就不会长久。

意识到这一点,我的这个博客以后可能会有些改变,更“自我”一些,并非是公布隐私,是公布思想,想法,一些科学经历。

这是最近发表在JBC上的一篇长文(12页)的摘要,这项工作用了大约3年的时间。一开始,老板有很多SUR1基因敲除的老鼠,养动物花费太高,决定快速减少老鼠账单的数,于是开始了这个我相信目前世界上只有我才(能?)完成的实验,每天从20只老鼠的胰腺里分离胰岛,培养,然后做一次要5000个胰岛的实验。

一开始的结果,谁也看不懂,于是实验就停了下来,后来我准备参加一个会议,要准备一个摘要,把实验结果翻出来,重新思考了SUR1基因敲除老鼠胰岛,GABA水平非常低的问题。于是我们决定用13C葡萄糖作为示踪物,看13C在胰岛里的流通情况。实验依旧很复杂,需要体力和精力的双重准备。结果,就是摘要里说明的情况。

算下来,这个实验共用胰岛大约6万个(8年时间,我大约分离了至少50万个老鼠胰岛了)。

Elimination of KATP channels in mouse islets results in elevated [U-13C]glucose metabolism, glutaminolysis and pyruvate cycling but decreased a GABA shunt.

Pancreatic beta-cells are hyper-responsive to amino acids but have decreased glucose sensitivity following deletion of the sulfonylurea receptor 1 (SUR1) both in man and mouse. It was hypothesized that these defects are the consequence of impaired integration of amino acid, glucose and energy metabolism in beta-cells. We used gas chromatography-mass spectrometry methodology to study intermediary metabolism of SUR1 knockout (SUR1-/-) and control mouse islets with [U-(13)C]-D-glucose as substrate and related the results to insulin secretion. The levels and isotope labeling of alanine, aspartate, glutamate, glutamine and gamma-aminobutyric acid (GABA) served as indicators of intermediary metabolism. We found that the GABA shunt of SUR1-/- islets is blocked by about 75% and showed that this defect is due to decreased glutamate decarboxylase (GAD) synthesis, probably caused by elevated free intracellular calcium. Glutaminolysis stimulated by the leucine analogue BCH was, however, enhanced in SUR1-/- and glyburide treated SUR1+/+ islets. Glucose oxidation and pyruvate cycling was increased in SUR1-/- islets at low glucose but was the same as in controls at high glucose. Malic enzyme isoforms 1, 2 and 3, involved in pyruvate cycling were all expressed in islets. High glucose lowered aspartate and stimulated glutamine synthesis similarly in controls and SUR1-/- islets. The data suggest that the interruption of the GABA shunt and the lack of glucose regulation of pyruvate cycling may cause the glucose insensitivity of the SUR1-/- islets but that enhanced basal pyruvate cycling, lowered GABA shunt flux and enhanced glutaminolytic capacity may sensitize the beta-cells to amino acid stimulation.





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发表评论?

4 条评论。

  1. 恭喜研究获得阶段性成果。

  2. 其实很矛盾吧,我也想过这个问题。我觉得,博客首先是为自己而写,然后才是传递价值和信息。博客也正因为有了一些个人的故事,才让人感觉到博客的温度,这种温度让人感到温暖。由此才体现博客的价值。否则,一个没有任何个人影子的博客,我倒觉得不像博客,那只是一些人用来盈利的工具,纯粹的传递价值、信息的工具。这样的博客很多人任何人都可以建立,而带有个人气息的博客,带着博主淡淡的体温,是无可复制的。所以,博客应该自我一些。我大胆的预测,除了那些单纯为盈利,并最终有良好经济循环的博客外,其他单纯传递信息,而博主的特色不是很浓的博客,终将关闭,最长不会挺过人的心理厌烦期–3年。而且以您的科学经历和素养,我们的确还有很多学习的地方。我曾经进去仔细想过,博客长久下去,还是博主的个人素质在起决定性作用。博主对生活的热爱,对技术的追求,还有博主写文字的能力(这种能力不应该成为一种负担),这些决定了博客的生存期。

    • 非常同意你的观点,博客的热度一过,剩下的都是金子。表达自己的观点可能也有助于思考的风气和独立的思想。

  3. 我不懂,但能感觉到您的执着

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