用果蠅研究血糖和胃口之間的關係有可能解釋2型糖尿病人的消瘦 |
論文標題:Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11
期刊:Communications Biology
作者:Rupali Ugrankar, Pano Theodoropoulos, Fatih Akdemir, W. Mike Henne & Jonathan M. Graff
發表時間:2018/08/13
數字識別碼:10.1038/s42003-018-0109-4
原文連結:https://www.nature.com/articles/s42003-018-0109-4?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Molecular_Biology_and_Genetics-China&utm_campaign=NEWCOMMS_USG_JRCN_RL_sciencenet_SLC5A11_4th_Aug
據世界衛生組織統計,目前全球已有近十分之一的人口患有2型糖尿病,此情況已經達到大流行性病的水平,給各國政府帶來了嚴重的醫療和經濟負擔。2型糖尿病和多種慢性病,比如肥胖或高血壓的並發明顯增加了疾病治療和管理的難度。
正常人會針對高血糖釋放胰島素來增加身體對葡萄糖的吸收。但是糖尿病人會有胰島素抵抗,即細胞對胰島素的反應減少,所以需要身體釋放更多的胰島素來刺激葡萄糖的吸收。到了最後,當身體不再對胰島素有反應,高血糖的狀態會持續,然後滲透作用會導致過多的水分進入血液,所以病人會有高血壓、口渴、多尿等症狀。雖然前期和早期2型糖尿病人會多食,但是晚期2型糖尿病人則會消瘦和乏力。
雖然科學家們很早就已經有哺乳動物會用血糖水平控制胃口的設想,但是其機理一直不詳。在《通訊-生物學》發表的一項研究Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11 中,以Jonathan M. Graff 為首的德克薩斯大學西南醫學中心的團隊用果蠅做模型動物研究了這個問題。
用果蠅來研究糖尿病已是慣例。比起大小鼠,研究果蠅有許多優勢:生命周期短(21天),樣本量大,飼養和管理划算,基因操作簡單並可以同時研究多個突變。本篇文章的研究對象是變形之前的果蠅幼蟲,因為這個階段的的幼蟲行為統一,只有進食。
Graff博士的團隊發現,有高血糖的幼蟲不想進食。他們發現,果蠅的能量主要來源是海藻糖,而葡萄糖主要是用來控制身體機制,比如進食。這和葡萄糖在人體內又提供能源又有控制機制的作用有所不同。
由於以前的研究已經發現SLC5A11能控制飢餓,本文中Graff博士的團隊則研究了SLC5A11在糖尿病的範圍內的作用。他們發現胰島素和SLC5A11有可能參加葡萄糖控制的進食。這有可能解釋2型糖尿病人在晚期的消瘦:那時嚴重的胰島素抵抗導致並加重高血糖,而高血糖減少胃口,因此病人只好以分解體內的脂肪來獲取能量,便導致了迅速的消瘦。
作者們希望他們的研究能夠推進對進化論裡保守的機制,比如對飢餓和進食控制的研究。由於控制胃口對肥胖和糖尿病的惡化至關重要,這項研究有望幫助針對慢性病的管理。
摘要:In mammals, blood glucose levels likely play a role in appetite regulation yet the mechanisms underlying this phenomenon remain opaque. Mechanisms can often be explored from Drosophila genetic approaches. To determine if circulating sugars might be involved in Drosophilafeeding behaviors, we scored hemolymph glucose and trehalose, and food ingestion in larvae subjected to various diets, genetic mutations, or RNAi. We found that larvae with glucose elevations, hyperglycemia, have an aversion to feeding; however, trehalose levels do not track with feeding behavior. We further discovered that insulins and SLC5A11 may participate in glucose-regulated feeding. To see if food aversion might be an appropriate screening method for hyperglycemia candidates, we developed a food aversion screen to score larvae with abnormal feeding for glucose. We found that many feeding defective larvae have glucose elevations. These findings highlight intriguing roles for glucose in fly biology as a potential cue and regulator of appetite.
閱讀論文全文請訪問:https://www.nature.com/articles/s42003-018-0109-4?utm_source=Other_website&utm_medium=Website_links&utm_content=RenLi-Nature-Communications_Biology-Molecular_Biology_and_Genetics-China&utm_campaign=NEWCOMMS_USG_JRCN_RL_sciencenet_SLC5A11_4th_Aug
期刊介紹:Communications Biology is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the biological sciences. Research papers published by the journal represent significant advances bringing new biological insight to a specialized area of research.
來源:科學網
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