The goal of this pilot study is to test the feasibility of assessing how biological factors and chemical properties of sugars may influence metabolism and food reward in humans. The main questions it aims to answer are:
Can differences in appetitive responses and neural activations to sucrose (table sugar) and its chemical components (glucose and fructose) be measured and quantified?
Are there detectable differences in how combinations of sugars and non-nutritive sweeteners commonly found in our food supply influence appetitive responses and neural activation?
This study is a crossover design, meaning every participant will complete every condition. Participants will consume beverages containing sucrose, glucose, or fructose, which are each novelly flavored, 6 times within a week. During one of the consumption times, energy expenditure, carbohydrate oxidation, and blood glucose will be measured in the lab before and for 2 hours after consumption. After participants have consumed each condition, they will undergo a tasting task in the MRI scanner, neural responses to receipt of the beverages are measured. Another group of participants will undergo the same study design but with sucrose, high fructose corn syrup, or sucrose + non-nutritive sweetener as the conditions.

开始日期2023-09-01

申办/合作机构

Virginia Polytechnic Institute & State University

NL-OMON51729 / SuspendedN/A

Effect of diEtaRy fructose on fructose kinetics in type 2 dIabetEs - ERIE

开始日期2022-10-01

申办/合作机构-

100 项与果糖相关的临床结果

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100 项与果糖相关的转化医学

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100 项与果糖相关的专利（医药）

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4,278

项与果糖相关的文献（医药）

2024-07-01·Food chemistry. Molecular sciences

Combined transcriptome and metabolome analysis of sugar and fatty acid of aromatic coconut and non-aromatic coconut in China

Article

作者: Li, Jing ; Zhou, Lixia ; Iqbal, Amjad ; Yang, Yaodong ; Sun, Xiwei ; Yarra, Rajesh ; Wu, Qiufei

Sugar and fatty acid content are among the important factors that contribute to the intensity of flavor in aromatic coconut. Gaining a comprehensive understanding of the sugar and fatty acid metabolites in the flesh of aromatic coconuts, along with identifying the key synthetic genes, is of significant importance for improving the development of desirable character traits in these coconuts. However, the related conjoint analysis of metabolic targets and molecular synthesis mechanisms has not been carried out in aromatic coconut until now. UPLC-MS/MS combined with RNA-Seq were performed in aromatic coconut (AC) and non-aromatic coconut (NAC) meat at 7, 9 and 11 months. The results showed that D-fructose in AC coconut meat was 3.48, 2.56 and 3.45 fold higher than that in NAC coconut meat. Similarly, D-glucose in AC coconut meat was 2.48, 2.25 and 3.91 fold higher than that in NAC coconut meat. The NAC coconut meat showed a 1.22-fold rise in the content of lauric acid compared to the AC coconut meat when it reached 11 months of age. Myristic acid content in NAC coconut meat was 1.47, 1.44 and 1.13 fold higher than that in AC coconut meat. The palmitic acid content in NAC coconut meat was 1.62 and 1.34 fold higher than that in AC coconut meat. The genes SPS, GAE, GALE, GLCAK, UGE, UGDH, FBP, GMLS, PFK, GPI, RHM, ACC, FabF, FatA, FabG, and FabI exhibited a negative correlation with D-fructose (r = -0.81) and D-glucose (r = -0.99) contents, while showing a positive correlation (r = 0.85-0.96) with lauric acid and myristic acid. Furthermore, GALE, GLCAK, FBP, GMLS, and ACC displayed a positive correlation (r = 0.83-0.94) with palmitic acid content. The sugar/organic acid ratio exhibited a positive correlation with SPS, GAE, UGE, FabF, FabZ and FabI.

2024-06-01·Food science and biotechnology

Structural and functional properties of Maillard-reacted casein phosphopeptides with different carbohydrates

Article

作者: Cao, Yu ; Lu, Yuping ; Cai, Zhipeng ; Zhu, Liqin ; Zheng, Haoyang ; Shen, Yonggen ; Chen, Kunlin ; Wang, Jing ; Chen, Ming ; Yuan, Meng

Graphical Abstract:

2024-05-01·Food chemistry

Enhancing physicochemical and functional properties of myo-inositol in crystallization with edible sugar additives

Article

作者: Li, Kangli ; Zhang, Leida ; Wei, Xuemei ; Gong, Junbo ; Wang, Xiaowei ; Shen, Runpu ; Zhao, Wei ; Chen, Mingyang ; Han, Dandan

Myo-inositol, referred to as vitamin B8, is an essential nutrient for maintaining human physiological functions. However, the morphology of myo-inositol products is predominantly powder or needle shaped, leading to poor food properties. In this work, three edible sugar additives, i.e. d-glucose, l-arabinose and d-fructose, are adopted in the crystallization of myo-inositol to improve its food properties. The results show that these additives change the morphology of myo-inositol crystals. d-glucose and l-arabinose reduced the aspect ratio of myo-inositol crystals, and d-glucose transformed elongated lamellar myo-inositol crystals into diamond-shaped lamellar crystals. The diamond-shaped lamellar myo-inositol products exhibited outstanding functional food properties. It offered a smoother texture and more pleasant mouthfeel when the products were added to infant formulas and nutraceuticals. When they were applied to functional beverages, the dissolution rate was increased by 35 %. This work provides a theoretical guidance for improving food properties through crystallization and possesses considerable potential for industrialization.

项与果糖相关的新闻（医药）

2024-06-22

·生物探索

Cell Research丨林圣彩课题组揭示机体碳源利用转换的新机制

引言葡萄糖、脂肪酸和氨基酸是生物体的三大碳源物质，是我们人体最重要也是最基本的物质与能量的来源，并调节了诸多生物学功能。然而，在日常生活中，三大碳源并非一直都很丰富，在许多条件下，例如在餐后数小时后或进餐之前，血糖以及组织中的葡萄糖水平都会显著地下降——这是十分常见的生理现象。尽管有糖原分解、糖异生等方式来补充葡萄糖，但这些过程至多保证机体血糖不会过低，从而防止出现低血糖等危及生命的状态，却不能完全阻止体内糖的短缺。因此，在面对血糖水平下降时，机体从主要利用葡萄糖到利用其它营养物的转变过程，就显得十分关键了。从上世纪50年代起，以George F Cahill Jr等为代表的先驱们，逐步揭示了饥饿条件下，机体能够动员所储存的脂肪（如脂肪组织里的甘油三酯）和蛋白质（如肌肉里的肌纤维），并利用被动员的脂肪酸、氨基酸进入线粒体中的三羧酸循环而被氧化，来弥补葡萄糖的短缺的现象，从而初步揭示了三大碳源物质之间，尤其是脂肪酸和氨基酸作为葡萄糖的替代碳源的利用与转化的规律【1】。后续的研究进一步从分子水平揭示了以AMPK为代表的代谢稳态维持的核心蛋白，能够在葡萄糖水平下降的情况下，通过磷酸化脂肪酸合成的关键酶ACC（acetyl-CoA carboxylase），来抑制脂肪酸的合成，并促进更多的脂肪酸被氧化【2】。而在氨基酸方面，AMPK能够抑制机体里另一个合成代谢的“主管”——mTORC1【3】，阻止mTORC1所介导的蛋白质的合成，从而为机体保留更多的游离氨基酸以维持它们的氧化【4】。除mTORC1以外，AMPK也能通过自噬作用以促进蛋白质的水解，从而产生更多的游离氨基酸【5】。在游离氨基酸中，又以谷氨酰胺和丙氨酸最为关键，尤其是前者，不但是血液循环中最为丰富的氨基酸（在饥饿时占到了体内游离氨基酸的50%以上），同时也是机体动员、释放的氨基酸最终进入血液循环并被如肝脏等器官氧化利用之前所必需被转化成的氨基酸种类（例如，肌肉动员的支链氨基酸大部分通过通过转氨等途径转化为谷氨酰胺，再进入血液被利用），可谓是牵一发而动全身。然而，谷氨酰胺的氧化利用本身是如何被促进的，却一直不清楚。 2024年6月19日，厦门大学的林圣彩课题组在Cell Research杂志发表了题为AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine的文章，阐述了促进谷氨酰胺代谢的机制。他们发现，在低葡萄糖条件下，AMPK能够通过磷酸化一个新底物——PDZD8（PDZ domain-containing protein 8），促进机体对谷氨酰胺这一关键氨基酸的氧化利用。从而“补全”了AMPK促进氨基酸作为葡萄糖的一类替代碳源的机制的拼图。林圣彩课题组长期以来致力于营养物质的感知与AMPK的激活机制的研究，他们先前发现了细胞感知葡萄糖水平下降，并激活AMPK的溶酶体通路（林圣彩组Nature破解葡萄糖感受的新机制【6, 7】，也发现了该通路如何与其它通路协作，介导在低葡萄糖条件下mTORC1的抑制的机制（Cell Research丨林圣彩团队发现感知葡萄糖调控mTORC1的感受器和机制）【8, 9】。在此基础上，他们开始在体内、在动物水平上，分析机体对氨基酸和脂肪酸的利用。他们选择了通过稳定同位素标记的谷氨酰胺和棕榈酸（是用于检测脂肪酸氧化的代表之一）来进行实验，借此仔细地跟踪了不同的饥饿时长下，谷氨酰胺和棕榈酸的利用。他们惊奇地发现，小鼠饥饿时，机体对谷氨酰胺的利用显著早于棕榈酸，表现在饥饿8小时，亦即血糖刚下降不久时，标记的谷氨酰胺进入线粒体和三羧酸循环并被氧化的量就明显增多，而棕榈酸氧化的增多则需要在饥饿12小时以上才能被观察到。这一现象也存在于体外培养的细胞中。重要的是，不仅仅是棕榈酸的氧化的增加需要通过AMPK来介导，谷氨酰胺氧化增加的本身也是完全依赖于AMPK的，这说明，AMPK能够通过一种未知的机制，促进谷氨酰胺的氧化。作者们于是尝试解析这一机制。他们回忆起了19年，也是在Cell Research上，他们发表的一篇文章（Cell Res封面丨林圣彩团队全景式展示AMPK时空调控图谱）【10】。在这篇文章中他们无意中报道了一个现象：葡萄糖水平下降以后的细胞中的线粒体更倾向于结合在内质网上，形成更多的MAM（mitochondria-associated membranes，线粒体相关内质网膜）结构，这表现在直接通过亚细胞分离（subcellular fractionation）的方法对细胞的膜结构进行纯化，所得到MAM组分，或者说MAM的“产量”明显增加，而不和内质网相互作用的、纯的线粒体的产量则显著降低。鉴于MAM对于线粒体的活力十分重要，作者们进一步对该现象进行了分析，发现低糖条件下，MAM组分的增加是依赖于AMPK的，并通过进一步用特异性地识别AMPK的磷酸化底物的抗体进行分析，确定了MAM组分中含有AMPK的底物。在此基础上，通过用此抗体对AMPK的底物进行富集，并辅助以蛋白质谱进行鉴定，他们发现了12个定位在MAM的，在低糖时被磷酸化的蛋白质。其中有3个——PDZD8、RMDN3和PDHA1，被进一步验证为AMPK的底物（其中PDHA1已被报道为AMPK的底物【11】）。通过分别敲除这三个基因，他们发现仅有PDZD8的敲除，能够阻止低糖所促进的谷氨酰胺氧化。进一步的探究发现了PDZD8被AMPK磷酸化的位点是其第527位的苏氨酸（T527），且在PDZD8敲除的细胞或者小鼠的肌肉中回补PDZD8-T527A突变体、阻断了AMPK对PDZD8的磷酸化以后，能够起到类似于PDZD8敲除以后的、阻止低糖所促进的谷氨酰胺氧化的作用。作者们还发现，PDZD8-T527A既不会反过来影响AMPK的激活，也不会影响AMPK对脂肪酸氧化的促进，这说明PDZD8是一个类比于ACC的、专门负责谷氨酰胺氧化这一功能的、AMPK的底物。作者还探究了PDZD8被AMPK磷酸化后，促进谷氨酰胺利用的机制。他们发现，在葡萄糖饥饿的细胞中，谷氨酰胺氧化的限速酶GLS1（glutaminase 1）的活力明显提高，并且高度依赖于AMPK对PDZD8的磷酸化。进一步的研究表明，AMPK对PDZD8的磷酸化能够促进后者的变构，使之加强与GLS1的相互作用，而这一相互作用显著地促进了GLS1的活力。在体外，把已经被AMPK磷酸化过的PDZD8蛋白与GLS1蛋白直接混合，就能够提升GLS1的活力。而突变了能够介导PDZD8与GLS1相互作用的氨基酸，就如同PDZD8-T527A一样，失去了激活GLS1乃至于饥饿时所加强的谷氨酰胺利用的作用。由此，作者们解析出了一条AMPK-PDZD8-GLS1的通路，通过该通路，机体能够在缺乏葡萄糖的条件下，动用谷氨酰胺以弥补葡萄糖缺乏所造成的影响。 AMPK通过PDZD8，促进GLS1和谷氨酰胺的代谢（Credit: Cell Research）作者们还将AMPK-PDZD8-GLS1促进谷氨酰胺代谢的通路与AMPK-ACC促进脂肪氧化的通路进行了比较，对后者动用脂肪酸的速度比前者动用谷氨酰胺的速度更加迟缓的现象做出了初步的解释。与AMPK-PDZD8-GLS1直接作用于线粒体的谷氨酰胺氧化不同，AMPK-ACC对脂肪酸氧化的促进是间接的：需要AMPK磷酸化并抑制ACC足够长的时间才能使得ACC的产物malonyl-CoA的水平下降到一定的水平，才能解除malonyl-CoA对线粒体脂肪酸氧化的抑制作用，才能够提升脂肪酸氧化的水平。而这一点在低糖条件下，溶酶体通路所介导的AMPK激活中更甚：此时AMPK的激活具有很强的区域性（集中在溶酶体上），且只能磷酸化并抑制定位在细胞质里的ACC1亚型【10】，通过细胞质内整体的malonyl-CoA水平的缓慢下降，传导到线粒体附近，最终促进脂肪酸的氧化。相比之下，如果通过使用激动剂无差别地激活胞内所有的AMPK，并在ACC1的基础上，同时引起定位在线粒体表面的ACC2的磷酸化，就能够通过局部地降低线粒体附近的malonyl-CoA，大大加快脂肪酸氧化的速度，使之被提升的时间点提前到和谷氨酰胺差不多的程度。当然，优先利用谷氨酰胺本身可能还有其它的生理意义，如分解损坏和剩余的蛋白质可能是组织更新的重要一环，而脂肪则是为长期饥饿而储备的。最后，作者还探究了AMPK-PDZD8-GLS1通路的生物学功能。有意思的是，该通路的缺乏并不影响低糖时细胞ATP的水平，这说明缺糖早期，细胞能够通过AMPK抑制蛋白合成等耗能的代谢途径，即使在没有谷氨酰胺氧化加强的条件下，有效地维持ATP的水平，直到缺糖后期脂肪酸氧化供能的加强。这也进一步暗示了谷氨酰胺氧化的加强可能有独特的生物学意义。作者们于是选择了LPS（lipopolysaccharides）所模拟的细菌急性感染的条件——该条件能够显著地降低血糖【12】，且GLS1和谷氨酰胺的利用已被证明对于机体响应LPS，启动免疫反应至关重要【13】。在致死剂量LPS处理的条件下，他们确实观察AMPK-PDZD8-GLS1 信号传递轴可以维持巨噬细胞对促炎因子的分泌，促进炎症反应的发生，并引起小鼠更严重的死亡。而在巨噬细胞中导入不能磷酸化的PDZD8-T527A突变体，则显著降低了机体针对LPS的炎症反应。尽管由于LPS的特殊性和急性炎症的特点，加强谷氨酰胺的利用反而加大了LPS的致死性——这和诸多感染条件下所发生的炎症反应所起到的保护作用相悖，但上述表型至少说明了AMPK-PDZD8-GLS1通路在低糖条件下的重要生理功能，对不同的临床患者是否添补谷氨酰胺的水平将会起到指导作用。该表型也进一步激发起我们在未来，对更长的时间尺度下的低糖和AMPK激活条件，如卡路里限制等条件下，谷氨酰胺代谢的重要功能的猜想与兴趣。总之，林圣彩课题组的发现解决了碳源代谢与调控方面的又一生物学重大机制，这一发现对我们认识机体维持代谢稳态与能量平衡，乃至未来对代谢紊乱的控制与“纠偏”，具有重要的启发意义。参考文献 1 Cahill GF, Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006;26:1-22. 2 Davies SP, Sim AT, Hardie DG. Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase [Comparative Study Research Support, Non-U.S. Gov't] [in eng]. Eur J Biochem 1990;187:183-190. 3 Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003;115:577-590. 4 Krause U, Bertrand L, Hue L. Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes. Eur J Biochem 2002;269:3751-3759. 5 Meley D, Bauvy C, Houben-Weerts JH et al. AMP-activated protein kinase and the regulation of autophagic proteolysis. The Journal of biological chemistry 2006;281:34870-34879. 6 Zhang CS, Hawley SA, Zong Y et al. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature 2017;548:112-116. 7 Li M, Zhang CS, Zong Y et al. Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK. Cell metabolism 2019;30:508-524 e512. 8 Zhang CS, Jiang B, Li M et al. The lysosomal v-ATPase-Ragulator complex Is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism. Cell Metab 2014;20:526-540. 9 Li M, Zhang CS, Feng JW et al. Aldolase is a sensor for both low and high glucose, linking to AMPK and mTORC1. Cell Res 2020. 10 Zong Y, Zhang CS, Li M et al. Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress. Cell Res 2019;29:460-473. 11 Cai Z, Li CF, Han F et al. Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis. Molecular cell 2020;80:263-278 e267. 12 Raetzsch CF, Brooks NL, Alderman JM et al. Lipopolysaccharide inhibition of glucose production through the Toll-like receptor-4, myeloid differentiation factor 88, and nuclear factor kappa b pathway. Hepatology 2009;50:592-600. 13 Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis. Signal Transduct Target Ther 2021;6:407. https://doi-org.libproxy1.nus.edu.sg/10.1038/s41422-024-00985-6 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

2024-03-30

·生物探索

Nat Chem Biol | 浙江大学吕志民/许大千揭示代谢酶FBP1调控端粒长度与细胞衰老决定肿瘤生长的新机制

引言端粒功能障碍与衰老过程错综复杂地联系在一起，并作为一个突出的癌症标志而突出。2024年3月27日，浙江大学吕志民及许大千共同通讯在Nature Chemical Biology在线发表题为“Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression”的研究论文，该研究证明端粒酶活性在癌症细胞和正常细胞中受到不同的调节，这取决于果糖-1,6-双磷酸酶1 (FBP1)的表达状态。在表达FBP1的细胞中，FBP1直接与端粒酶逆转录酶(TERT)的Ser227位点相互作用并使其去磷酸化。去磷酸化的TERT无法转位到细胞核中，导致小鼠端粒酶活性受到抑制，端粒长度减少，衰老加剧，肿瘤细胞增殖和生长受到抑制。脂质纳米颗粒介导的FBP1 mRNA递送抑制肝脏肿瘤生长。此外，在肾癌和肝癌标本中，FBP1表达水平与TERT pSer227水平呈负相关，并与患者预后不良相关。这些发现表明，FBP1通过其蛋白磷酸酶活性来控制细胞的不朽，并揭示了肿瘤细胞中由于FBP1表达下调或缺乏而产生的独特的端粒酶调节。端粒由重复的TTAGGG核苷酸序列组成，形成一个“帽状结构”，其功能是维持染色体的完整性。端粒在每一轮DNA复制过程中逐渐缩短，端粒功能的丧失导致有丝分裂期间染色体端到端融合，导致双中心染色体的形成和随后染色体断裂的后期桥接。生成的两个子细胞接受不均匀的染色单体，含有两个缺乏端粒的染色单体，导致有丝分裂后的断裂-融合桥(BFB)周期，最终导致正常细胞衰老和凋亡。在癌细胞中，端粒伸长和长度主要依赖于高度激活的端粒酶，在大多数人类癌症中，端粒酶合成端粒重复序列，在5-15%的癌症中，端粒选择性延长(ALT)。端粒酶的活性受端粒酶逆转录酶(TERT)的调控，TERT是端粒酶的催化蛋白亚基，在转录水平和翻译后水平均受调控。TERT磷酸化显著增加端粒酶活性。用于组装具有催化活性的端粒酶，细胞质TERT必须转运到细胞核中，这一过程需要AKT介导的TERT Ser227磷酸化才能将输入蛋白α与TERT8的核定位信号结合。然而，TERT磷酸化和随后的端粒功能在正常细胞和癌细胞中是否受到不同的调节，这在很大程度上是未知的。果糖-1,6-二磷酸酶1 (FBPase 1)是糖异生过程中的限速酶，可将果糖-1,6-二磷酸(F1,6BP)水解为果糖- 6-磷酸(F6P)。在哺乳动物中，两个独立的基因，FBP1和FBP2，分别编码肝脏和肌肉中FBPase的亚型。FBP1主要表达于肝脏和肾脏，在几乎100%的透明细胞肾细胞癌(ccRCC)中普遍缺失，在肝细胞癌(HCC)和其他类型的癌症中经常下调。它的缺乏促进了肝脏肿瘤的进展，并与较差的总生存率和较高的肿瘤复发率相关。研究表明，FBP1与HCC和ccRCC细胞中的缺氧诱导因子(HIFs)或增强子zeste同源物2 (EZH2)以酶活性不依赖的方式相互作用并抑制HIFs。此外，FBP1作为蛋白磷酸酶去磷酸化组蛋白H3来调节基因表达。然而，FBP1的酶活性是否具有直接调节肿瘤细胞增殖的兼职功能尚不清楚。、模式图（Credit: Nature Chemical Biology）该研究证明了FBP1通过FBP1的疏水残基N273与TERT相互作用。FBP1作为蛋白磷酸酶，使TERT的S227位点(pS227)去磷酸化，从而抑制TERT核易位和端粒酶活性，减少端粒长度，抑制肿瘤细胞的增殖和衰老。FBP1蛋白磷酸酶死亡突变体的表达促进了小鼠肿瘤的生长，同时TERT S227磷酸化水平和端粒长度增加。该研究揭示了FBP1蛋白磷酸酶活性对肿瘤和正常细胞中TERT活性差异调节的一个未知的关键机制。低FBP1表达与高TERT S227磷酸化水平以及较短的ccRCC和HCC患者生存期呈负相关，结合lnp为基础的FBP1 mRNA递送有效抑制肿瘤生长，强调了调节蛋白磷酸酶活性和FBP1表达以治疗人类癌症的潜力。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41589-024-01597-2责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

信使RNA临床结果

2024-03-06

·Science Daily

The sweet stuff: How insects tell sugars apart

Whereas humans have one receptor on their tongues that can detect all sorts of sweet things, from real sugar to artificial sweeteners like aspartame, insects have many receptors that each detect specific types of sugars. Researchers have now uncovered one way insect receptors are able to be so selective, an insight they say will help us understand how animals decipher the chemical world and how we might mimic that ability in the future. Whereas humans have one receptor on their tongues that can detect all sorts of sweet things, from real sugar to artificial sweeteners like aspartame, insects have many receptors that each detect specific types of sugars. Yale researchers have now uncovered one way insect receptors are able to be so selective, an insight they say will help us understand how animals decipher the chemical world and how we might mimic that ability in the future. They reported their findings in a study published March 6 in Nature. Sugar is important to animals and humans alike, says Joel Butterwick, assistant professor of pharmacology at Yale School of Medicine and senior author of the study. "We all taste sugar. It's a major source of energy for just about every animal," said Butterwick. The ability to taste sugar is also essential for identifying necessary nutrients and generating a pleasurable feeling that becomes paired with nourishment. Different than mammals, insects also rely on their taste system to detect mating partners and identify the best places to deposit their eggs. But just how insects detect specific sugars -- differentiating between molecules that look quite similar to each other but that have subtle differences -- has remained unclear. To better understand the sensitivity of insect taste receptors, Butterwick and his research team focused on one receptor that is so selective it responds to only one type of sugar -- D-fructose. The receptor is one found in the mouths and brains of silk moths. As a ligand-gated receptor, it becomes activated only after its ligand -- the molecule that's able to bind to it -- attaches. Unexpectedly, even though D-fructose is the only sugar that activates this receptor, the researchers found that several other sugars bind to it, the researchers said. "That told us that the area where these sugars attach, the binding pocket, isn't the only thing determining activation," said Butterwick. "There had to be some other explanation. So we wanted to look at the receptor at atomic scale to see in detail how the sugar and receptor were interacting." The team mapped the structure of the receptor alone as well as the receptor bound to D-fructose. They observed that D-fructose was nestled into the binding pocket and initiated a shape change that activated the receptor. They then mapped the structure of the receptor when it was bound to a sugar extremely similar to D-fructose. While that sugar, L-sorbose, did appear to bind to the receptor just as well as D-fructose, it didn't change the receptor's shape, leaving the receptor inactive. The difference between the two sugars turned out not to be how they attached to the binding pocket, but how they interacted with a molecular bridge that connects the binding pocket to a different part of the receptor. In short, D-fructose was able to engage that bridge and initiate the shape change, and L-sorbose was not. "What we think is interesting about that is that there are interactions happening outside of the pocket that act as a mechanism of selection," said Butterwick. "And evolution likely works on both aspects. For example, a less specific receptor than this one maybe binds more molecules or maybe its bridge is easier to activate. With multiple aspects to act upon, there are more ways for evolution to fine-tune these receptors." Uncovering the mechanisms that underlie how receptors recognize various substances will help researchers understand how smell and taste enable humans and animals to decipher the chemical world, says Butterwick. It could also inform the development of biosensors, he added. Some dogs can smell diseases like cancer or Parkinson's disease. Knowing how smell and taste receptors differentiate substances would aid the development of "electronic noses" that could sniff out disease. "People are already trying to do this. And while there have been a few successes, there have been more failures," said Butterwick. "Our work here may help explain why it has been challenging. It's not just about binding the molecule of interest. How the receptor activates is also essential." Going forward, the researchers want to explore the pharmacological potential of these receptors. "There have been countless cases throughout history where a solved atomic structure paved the way to major discoveries," said João Victor Gomes, a graduate student in Butterwick's lab and lead author of the study. Gomes is from Brazil, which is currently facing a severe dengue surge, with more than one million cases of the mosquito-borne disease registered this year alone. "If we can modulate receptors that affect the feeding behavior of insects," he said, "perhaps we could develop better strategies against disease-transmitting mosquitoes."

100 项与果糖相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00114	-	-	DB04173

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
糖尿病	日本	Otsuka Pharmaceutical Factory, Inc.	1985-03-18

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASN2016	N/A	脱水	-	Fructose	網膚壓鹹蓋願願鬱壓遞(艱壓範築顧簾鑰夢醖憲) = 醖壓積鏇淵蓋齋廠積積醖衊膚範鹹獵構壓遞衊 (鹽鑰鏇獵襯築繭壓齋憲 ) 更多	-	2016-11-15
				Fructose	獵顧簾製積構簾壓獵鏇(廠製鑰範鬱製選網顧範) = 糧遞製膚淵觸獵醖遞蓋衊獵膚窪襯窪壓鏇鏇觸 (築齋餘壓夢獵齋廠鹹鬱 ) 更多
NCT02068638 (EASD2016)	N/A	1型糖尿病	-	combined glucose-fructose supplementation	憲壓淵壓醖鹽觸顧鏇遞(艱範齋醖築艱廠選艱憲) = 鹹廠醖網網餘製願願遞繭襯觸簾鹹齋膚窪鏇觸 (鹽夢窪衊夢範膚廠鏇膚 ) 更多	积极	2016-09-13
				combined glucose-fructose supplementation	憲壓淵壓醖鹽觸顧鏇遞(艱範齋醖築艱廠選艱憲) = 製繭襯顧壓廠積簾積齋繭襯觸簾鹹齋膚窪鏇觸 (鹽夢窪衊夢範膚廠鏇膚 ) 更多
NCT01363791 (Pubmed \| J Am Heart Assoc)	N/A	痛风 \| 代谢综合征 \| 糖尿病前期 ... 更多	-	Fructose	鏇襯鏇製遞簾鬱廠積鹽(積廠選壓糧構夢遞齋鹹): P-Value = 0.18 mmol/L 更多	-	2015-09-10
				fructose (Control carbohydrate)
NCT01363791 (Pubmed \| Diabetes Care)	N/A	糖尿病	209	Fructose	醖齋蓋獵積鬱遞窪夢鹹(夢鹹憲積鹽遞壓構餘鏇): SMD = -0.25 (95% CI, -0.46 ~ -0.04), P-Value = 0.02 更多	-	2012-07-01
				fructose (Carbohydrate)
NCT01363791 (Pubmed \| J Nutr)	N/A	-	425	Fructose	糧鏇壓糧網築窪網壓觸(窪顧選衊蓋夢鹽選選築) = 顧鬱壓夢餘廠齋襯鏇夢顧齋衊膚夢憲艱糧範窪 (遞醖醖窪願淵膚觸艱選, -6.62, 7.74) 更多	-	2012-05-01
ASN2010	N/A	代谢综合征	-	Fructose	繭鑰築壓簾夢襯艱廠餘(鏇窪艱顧襯餘製鑰願糧) = 網齋淵獵製衊餘淵窪鹽選淵憲憲願衊顧醖簾齋 (獵顧齋窪鏇顧糧艱醖觸 ) 更多	积极	2010-11-16