生物谷報道：紐約大學和Scripps研究所的研究人員發(fā)現(xiàn)了一種稱為GAPDH的酶,，能夠調(diào)節(jié)胰島素通路――這個發(fā)現(xiàn)為治療糖尿病提供了新方向,。這一研究在最新一期自然.化學生物學雜志上有所報道,。
以前并不知道GAPDH這種酶是人產(chǎn)生糖尿病的因素之一，現(xiàn)在,，該研究還發(fā)現(xiàn),，抑制GAPDH的活性能減輕動物模型的糖尿病癥狀,。
該研究隊伍來自紐約大學生物學與化學系和Scripps細胞生物學部,，他們用秀麗隱桿線蟲（C.elegans）來分離鑒定治療糖尿病的新的靶點蛋白,。秀麗隱桿線蟲是第一個被發(fā)現(xiàn)存在RNA干擾（RNAi）的動物，也是研究化學遺傳學的很好的模式生物,。在該研究中,，研究人員用糖尿病突變株作為糖尿病模型，從秀麗隱桿線蟲身上上百種化合物中篩選一種能夠讓糖尿病秀麗隱桿線蟲存活的化合物,。于是,，他們找到了目標蛋白――GAPDH酶?？茖W家很早就知道GAPDH是一種重要的糖酵解酶,，而且它的功能是受胰島素影響的。然而,，這是首次發(fā)現(xiàn)GAPDH能積極的調(diào)節(jié)胰島素通路。
雖然市場上已經(jīng)有很多治療糖尿病的藥物,，但是已知的產(chǎn)生糖尿病的蛋白靶點的數(shù)目是不多的,。因為糖尿病是多因素產(chǎn)生的，針對幾個不同的蛋白進行治療是最有希望的治療方法,。GAPDH的發(fā)現(xiàn)為該疾病的聯(lián)合治療添加了又一靶點,。
英文原文：
NYU, Scripps Finding Offers New Path for Treatment of Diabetes
11/27/06 -- Researchers at New York University and the Scripps Research Institute have discovered a new enzyme, GAPDH, which regulates insulin pathways--a finding that offers a new direction for the treatment of diabetes. The research is reported in the most recent issue of the journal Nature Chemical Biology.
The enzyme GAPDH was previously unknown to be a factor in the development of diabetes in humans. It has also been discovered that the inhibition of GAPDH attenuates the diabetic disease symptom in model animals.
The research team, which included NYU?s Departments of Biology and Chemistry and Scripps? Department of Cell Biology, used the worm Caenorhabditis elegans (C. elegans) to identify a new therapeutic target protein for diabetic treatment. C. elegans is the first animal species where RNA interference (RNAi) is discovered and thus, an excellent model organism for chemical genetic research. In this study, the researchers screened hundreds of chemical compounds to find one hit compound, which rescues the mutant C. elegans (diabetics model) from diabetes. Then, they identified the target protein, which was found to be the enzyme GAPDH. GAPDH has long been known as one of the important glycolytic enzymes, and its function is affected by insulin. However, this is the first discovery that GAPDH actively regulates the insulin pathway.
The research team constructed all the molecules by incorporating the fishing tag (linker) from the beginning, and facilitated the target fishing. The hit compound was named GAPDS (GAPDH segregator) as GAPDS disassemble the multi-part structure of GAPDH into monomers. The segregation of GAPDH releases the suppressor of insulin signaling from the cell membrane, and thus activates the insulin signaling to eventually help to treat diabetes.
While the C-elegans is a recommended model for chemical genetic study, treating them with chemical compounds presented difficulties for the researchers because they grow on the surface of agar. To overcome these challenges, the researchers devised a soaking method in which the worms were placed in a compound solution for 24 hours. By this method, the worms were exposed to equitable concentration of the compounds. The mutant C-elegans are in a growth arrested status. By addition of compounds, a re-growing of the worms into normal size was observed by GAPDS, which is analogous to treating diabetes patients with a drug.
While there are many drugs on the market to treat diabetes, the number of known disease-producing protein targets is small. Because diabetes has many causes, targeting several different proteins offers the most promising method for treatment. The discovery of GAPDH adds another target that can be addressed in combating the disease.
Source: New York University
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