Regulation of B-type natriuretic peptide synthesis by insulin in obesity in male mice.
Regulation of B-type natriuretic peptide synthesis by insulin in obesity in male mice.
复制标题
胰岛素对肥胖雄性小鼠 B 型利尿钠肽合成的调节。
DOI：
10.1113/ep085091
复制
发表时间：
2016
影响因子：
2.7
通讯作者：
Scherrer-Crosbie,Marielle
中科院分区：
文献类型：
--
作者：
Zhang,Haihua;Thoonen,Robrecht;Yao,Vincent;Buys,EmmanuelS;Popovich,John;Su,YanRu;Wang,ThomasJ;Scherrer-Crosbie,Marielle
新发现这项研究的中心问题是什么？脑钠肽（BNP）的血浆浓度在肥胖中降低，这一发现从心血管、肾脏和代谢的角度来看可能是有害的。本研究使用高果糖、高脂肪（HFHF）饮食小鼠模型和分离的心肌细胞来研究这种减少的机制。主要发现是什么及其重要性？在喂食HFHF 4周的小鼠左心室和长时间暴露于高剂量胰岛素的心肌细胞中，BNP基因表达水平降低。BNP合成的减少可能导致肥胖和胰岛素抵抗中BNP血浆浓度的降低。人类研究表明，胰岛素抵抗和肥胖与B型利钠肽（BNP）血浆浓度降低有关。该研究的目的是深入了解胰岛素抵抗和BNP血浆浓度降低之间的关联机制。喂食高脂肪、高果糖（HFHF）饮食4周的小鼠出现轻度肥胖和全身胰岛素抵抗。血浆中胰岛素、葡萄糖和甘油三酯浓度升高。HFHF饮食还与心肌胰岛素抵抗有关，其特征是左心室磷酸肌肽3 -激酶- akt （PI3K-AKT）通路对胰岛素的反应受损。与对照组相比，hhff喂养小鼠心肌BNP表达和蛋白水平降低。将心肌细胞暴露于100 nm胰岛素下，激活PI3K-AKT信号传导（15分钟），诱导bnpgene表达增加1.9±0.3倍（6小时）。心肌细胞长时间暴露于高胰岛素浓度（100 nm） 48小时诱导胰岛素抵抗，其特征是PI3K-AKT信号通路反应受损，bnpgene表达对胰岛素的反应降低。用PI3激酶抑制剂（wortmannin）处理心肌细胞7小时，可以重现bnpgene表达的降低。综上所述，HFHF饮食在体内、长期暴露于胰岛素浓度升高或抑制PI3K-AKT通路均可降低bnpmrna水平；这种减少可能反过来有助于胰岛素抵抗个体血浆中BNP肽浓度的降低。
New FindingsWhat is the central question of this study?The plasma concentration of brain natriuretic peptide (BNP) is decreased in obesity, a finding that may be deleterious from a cardiovascular, renal and metabolic standpoint. The present study used a mouse model of high‐fructose, high‐fat (HFHF) diet and isolated cardiomyocytes to investigate the mechanisms involved in this decrease.What is the main finding and its importance?The gene expression level of BNP is decreased in the left ventricle of mice fed a HFHF diet for 4 weeks and in cardiomyocytes exposed to prolonged high doses of insulin. A decrease in BNP synthesis may contribute to the decreased BNP plasma concentrations observed in obesity and insulin resistance.Human studies suggest that insulin resistance and obesity are associated with a decrease in B‐type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high‐fat, high‐fructose (HFHF) diet for 4 weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide 3‐kinase–AKT (PI3K–AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF‐fed mice compared with control animals. Exposure of cardiomyocytes to 100 nminsulin activated PI3K–AKT signalling (15 min) and induced a 1.9 ± 0.3‐fold increase inBNPgene expression (6 h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100 nm) for 48 h induced insulin resistance, characterized by an impaired response of the PI3K–AKT signalling pathway and a decreased response of theBNPgene expression to insulin. The decreased response inBNPgene expression was reproduced by treating cardiomyocytes for 7 h with a PI3‐kinase inhibitor (wortmannin). In conclusion, HFHF dietin vivo, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K–AKT pathwayin vitroall decreaseBNPmRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin‐resistant individuals.
登录
查看更多内容
选择两种治疗方法之一的模型
影响因子：
3.7
作者：
T. Colton
通讯作者：
T. Colton
临床试验的两阶段设计。
DOI：
--
发表时间：
1969
期刊：
影响因子：
--
作者：
Day Ne
通讯作者：
Day Ne
序贯药物筛选中的最佳复制
DOI：
--
发表时间：
1964
期刊：
影响因子：
--
作者：
E. King
通讯作者：
E. King
影响因子：
1.9
作者：
COLTON, T
通讯作者：
COLTON, T
对癌症 II 期试验的统计贡献：解释、分析和设计。
DOI：
--
发表时间：
1981
期刊：
影响因子：
--
作者：
Lee Yj;W. Ra
通讯作者：
W. Ra