Glucose and Insulin Differently Regulate Gluconeogenic and Ureagenic Gene Expression.

IF 0.7 4区 医学 Q4 NUTRITION & DIETETICS
Kanako Deguchi, Chihiro Ushiroda, Yuka Kamei, Kyosuke Kondo, Hiromi Tsuchida, Yusuke Seino, Daisuke Yabe, Atsushi Suzuki, Shizuko Nagao, Katsumi Iizuka
{"title":"Glucose and Insulin Differently Regulate Gluconeogenic and Ureagenic Gene Expression.","authors":"Kanako Deguchi, Chihiro Ushiroda, Yuka Kamei, Kyosuke Kondo, Hiromi Tsuchida, Yusuke Seino, Daisuke Yabe, Atsushi Suzuki, Shizuko Nagao, Katsumi Iizuka","doi":"10.3177/jnsv.71.46","DOIUrl":null,"url":null,"abstract":"<p><p>Glucose and insulin positively regulate glycolysis and lipogenesis through the activation of carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP1c), but their respective roles in the regulation of gluconeogenic and ureagenic genes remain unclear. We compared the effects of the insulin antagonist S961 and Chrebp deletion on hepatic glycolytic, lipogenic, gluconeogenic, and ureagenic gene expression in mice. S961 markedly increased the plasma glucose, insulin, and 3-OH-butyrate concentrations and reduced the hepatic triglyceride content, but Chrebp deletion had no additive effect. We subsequently estimated the expression of genes involved in the pathways of glycolysis, gluconeogenesis, and lipogenesis. S961 potently decreased both Chrebp and Srebf1c, but Chrebp deletion weakly decreased Srebf1c mRNA expression. Both the S961 and Chrebp deletion caused decreases in glycolytic (Gck and Pklr) and lipogenic (Fasn, Scd1, Me1, Spot14, Elovl6) gene expression. S961 increased the expression of many gluconeogenic genes (G6pc, Fbp1, Aldob, Slc37a4, Pck), whereas Chrebp deletion reduced the expression of gluconeogenic genes other than Pck1. Finally, we checked the metabolites and gene expression in the ureagenesis pathway. S961 increased ureagenic gene (Arg1, Asl, Ass1, Cps1, Otc) expression, which was consistent with the metabolite data: there were reductions in the concentrations of glutamate and aspartate and increases in those of citrulline, ornithine, urea, and proline. However, Chrebp deletion had no additive effect on ureagenesis. In conclusion, insulin rather than glucose regulate ureagenic gene expression, whereas glucose and insulin regulate gluconegenic gene expression in opposite directions.</p>","PeriodicalId":16624,"journal":{"name":"Journal of nutritional science and vitaminology","volume":"71 1","pages":"46-54"},"PeriodicalIF":0.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of nutritional science and vitaminology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3177/jnsv.71.46","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0

Abstract

Glucose and insulin positively regulate glycolysis and lipogenesis through the activation of carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP1c), but their respective roles in the regulation of gluconeogenic and ureagenic genes remain unclear. We compared the effects of the insulin antagonist S961 and Chrebp deletion on hepatic glycolytic, lipogenic, gluconeogenic, and ureagenic gene expression in mice. S961 markedly increased the plasma glucose, insulin, and 3-OH-butyrate concentrations and reduced the hepatic triglyceride content, but Chrebp deletion had no additive effect. We subsequently estimated the expression of genes involved in the pathways of glycolysis, gluconeogenesis, and lipogenesis. S961 potently decreased both Chrebp and Srebf1c, but Chrebp deletion weakly decreased Srebf1c mRNA expression. Both the S961 and Chrebp deletion caused decreases in glycolytic (Gck and Pklr) and lipogenic (Fasn, Scd1, Me1, Spot14, Elovl6) gene expression. S961 increased the expression of many gluconeogenic genes (G6pc, Fbp1, Aldob, Slc37a4, Pck), whereas Chrebp deletion reduced the expression of gluconeogenic genes other than Pck1. Finally, we checked the metabolites and gene expression in the ureagenesis pathway. S961 increased ureagenic gene (Arg1, Asl, Ass1, Cps1, Otc) expression, which was consistent with the metabolite data: there were reductions in the concentrations of glutamate and aspartate and increases in those of citrulline, ornithine, urea, and proline. However, Chrebp deletion had no additive effect on ureagenesis. In conclusion, insulin rather than glucose regulate ureagenic gene expression, whereas glucose and insulin regulate gluconegenic gene expression in opposite directions.

葡萄糖和胰岛素对糖异生和尿原基因表达的调控不同。
葡萄糖和胰岛素通过激活碳水化合物反应元件结合蛋白(ChREBP)和甾醇调节元件结合蛋白1c (SREBP1c)正向调节糖酵解和脂肪生成,但它们各自在糖异生和致尿基因调控中的作用尚不清楚。我们比较了胰岛素拮抗剂S961和Chrebp缺失对小鼠肝糖酵解、脂肪生成、糖异生和脲原基因表达的影响。S961显著提高了血浆葡萄糖、胰岛素和3- oh -丁酸盐浓度,降低了肝脏甘油三酯含量,但Chrebp缺失无附加效应。我们随后估计了参与糖酵解、糖异生和脂肪生成途径的基因的表达。S961能有效地降低Chrebp和Srebf1c,但Chrebp缺失能微弱地降低Srebf1c mRNA的表达。S961和Chrebp缺失均导致糖酵解(Gck和plklr)和脂肪生成(Fasn, Scd1, Me1, Spot14, Elovl6)基因表达降低。S961增加了许多糖异生基因(G6pc、Fbp1、Aldob、Slc37a4、Pck)的表达,而Chrebp缺失减少了除Pck1以外的糖异生基因的表达。最后,我们检查了尿发生途径的代谢物和基因表达。S961增加了致尿基因(Arg1、Asl、Ass1、Cps1、Otc)的表达,这与代谢物数据一致:谷氨酸和天冬氨酸浓度降低,瓜氨酸、鸟氨酸、尿素和脯氨酸浓度升高。然而,Chrebp缺失对脲原性无附加效应。综上所述,胰岛素而不是葡萄糖调节致尿基因的表达,而葡萄糖和胰岛素调节糖原基因的表达方向相反。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
1.80
自引率
6.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Nutritional Science and Vitaminology is an international medium publishing in English of original work in all branches of nutritional science, food science and vitaminology from any country. Manuscripts submitted for publication should be as concise as possible and must be based on the results of original research or of original interpretation of existing knowledge not previously published. Although data may have been reported, in part, in preliminary or abstract form, a full report of such research is unacceptable if it has been or will be submitted for consideration by another journal.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信