Effects of intestinal luminal contents and the importance of microfold cells on the ability of cell-penetrating peptides to enhance epithelial permeation of insulin.
Effects of intestinal luminal contents and the importance of microfold cells on the ability of cell-penetrating peptides to enhance epithelial permeation of insulin.
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肠腔内容物的影响和微褶皱细胞对细胞穿透肽增强胰岛素上皮渗透能力的重要性。
DOI：
10.1016/j.ejpb.2020.08.001
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
M. Takeda
中科院分区：
文献类型：
--
作者：
N. Kamei;S. Kawano;R. Abe;Serena Hirano;Hideyuki Ogino;Hideyuki Tamiwa;M. Takeda
我们以前报道过，在大鼠和小鼠体内，与细胞穿透肽（CPP）共同给药可显著增强胰岛素的口服和肠道吸收。为了评价CPPs作为吸收促进剂的临床应用，有必要阐明CPPs体外渗透促进作用的相关机制。验证实验表明，CPP，如D-八精氨酸（D-R8）和L-穿透素，对胰岛素上皮渗透的体内和体外效应之间存在差异。本研究旨在确定在体内起作用但在由Caco-2细胞组成的体外系统中缺乏的因子。在禁食状态模拟肠液（FaSSIF）中，D-R8和L-penetratin对胰岛素透过Caco-2细胞单层的作用部分增强。与预期相反，CPP对细胞摄取胰岛素的影响以及通过表面等离子体共振分析的CPP与胰岛素在正常缓冲液和FaSSIF中的结合率是相似的。此外，CPP，特别是D-R8，对细胞摄取胰岛素的影响，在具有微折叠细胞（M细胞）样特性的Caco-2细胞单层中更强。这些结果表明，肠道脂质和M细胞在CPP对胰岛素在体内的净上皮渗透的刺激作用中起关键作用。
We previously reported that oral and intestinal absorption of insulin in rats and mice is significantly enhancedin vivoby coadministration with cell-penetrating peptides (CPPs). To evaluate the clinical use of CPPs as absorption enhancers, it is imperative to clarify the mechanisms associated with the permeation-stimulatory effect of CPPsin vitro. The confirmation experiment revealed a discrepancy betweenin vivoandin vitroeffects of CPPs, such as D-octaarginine (D-R8) and L-penetratin, on epithelial permeation of insulin. The present study was designed to determine the factors that workin vivobut are deficient in anin vitrosystem consisting of Caco-2 cells. The effects of D-R8 and L-penetratin on permeation of insulin through the Caco-2 cell monolayer were partially boosted in fasted-state simulated intestinal fluid (FaSSIF). Contrary to expectation, the effects of CPPs on cellular uptake of insulin and the binding ratio of CPPs to insulin analyzed by surface plasmon resonance in normal buffer and FaSSIF were similar. Also, the effects of CPPs, especially D-R8, on cellular uptake of insulin, were stronger in Caco-2 cell monolayers with microfold cell (M cell)–like properties. These results suggested a key role of intestinal lipids and M cells in the stimulatory effect of CPPs on net epithelial permeation of insulinin vivo.
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影响因子：
14
作者：
Krug, Susanne M.;Amasheh, Maren;Amasheh, Salah
通讯作者：
Amasheh, Salah
DOI：
10.1016/j.jconrel.2012.01.041
发表时间：
2012-05-30
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Loo Y;Grigsby CL;Yamanaka YJ;Chellappan MK;Jiang X;Mao HQ;Leong KW
通讯作者：
Leong KW
DOI：
10.1016/j.jconrel.2016.07.051
发表时间：
2016-09-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Banerjee A;Qi J;Gogoi R;Wong J;Mitragotri S
通讯作者：
Mitragotri S
影响因子：
3.8
作者：
Walter, E;Janich, S;Amidon, GL
通讯作者：
Amidon, GL