Influence of fed-fasted state on intestinal PEPT1 expression and in vivo pharmacokinetics of glycylsarcosine in wild-type and Pept1 knockout mice.
Influence of fed-fasted state on intestinal PEPT1 expression and in vivo pharmacokinetics of glycylsarcosine in wild-type and Pept1 knockout mice.
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DOI：
10.1007/s11095-011-0580-9
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发表时间：
2012-02
影响因子：
3.7
通讯作者：
Smith, David E.
中科院分区：
文献类型：
--
作者：
Ma, Ke;Hu, Yongjun;Smith, David E.
目的：观察口服甘氨酰肌氨酸(GlySar)后，禁食是否会影响PEPT1的肠道表达和体内功能活性。对野生型和Pept1基因敲除小鼠的全身暴露和组织分布进行了研究，在喂养和禁食条件下，静脉和口服剂量为5nmol/g体重的[14C]GlySar。用实时荧光定量聚合酶链式反应和免疫印迹法检测肠道PEPT1的表达。我们发现，在禁食期间，野生型小鼠小肠中PEPT1蛋白的表达比喂养条件下增加了~2倍。一致的是，在禁食和喂养状态下，野生型小鼠的全身暴露和口服GlySar的峰值血浆浓度分别高出40%和65%。在PEPT1消融期间，喂食和禁食动物之间没有显著差异。口服给药后，所有四个治疗组的GlySar的组织分布都没有变化。只要禁食16小时，就能显著上调小肠中PEPT1蛋白的表达，进而显著增加体内口服GlySar的吸收。
To determine if fasting would affect the intestinal expression and in vivo functional activity of PEPT1 as determined after oral dosing of the dipeptide glycylsarcosine (GlySar). Systemic exposure and tissue distribution studies were performed in wild-type and Pept1 knockout mice, under fed and fasted conditions, following both intravenous and oral doses of [14C]GlySar at 5 nmol/g body weight. Intestinal PEPT1 expression was evaluated by real-time PCR and immunoblot analyses. We found that expression of PEPT1 protein in the small intestine was increased ~2-fold in wild-type mice during fasted as compared to fed conditions. In agreement, systemic exposure and peak plasma concentrations of orally administered GlySar were 40 and 65% greater, respectively, in wild-type mice during fasted vs. fed state. No significant differences were observed between fed and fasted animals during PEPT1 ablation. Tissue distribution of GlySar was unchanged after oral dosing for all four treatment groups. As little as 16 hr of fasting can cause significant upregulation of PEPT1 protein expression in the small intestine, which then translates into a significant increase in in vivo oral absorption of GlySar.
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影响因子：
3.8
作者：
Ma, Katherine;Hu, Yongjun;Smith, David E.
通讯作者：
Smith, David E.
影响因子：
64.8
作者：
FEI, YJ;KANAI, Y;HEDIGER, MA
通讯作者：
HEDIGER, MA
影响因子：
3.9
作者：
Shen, Hong;Ocheltree, Scott M.;Smith, David E.
通讯作者：
Smith, David E.
DOI：
10.1152/ajpgi.00171.2006
发表时间：
2006-11-01
影响因子：
4.5
作者：
Shimakura, Jin;Terada, Tomohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
5.8
作者：
Shimakura, Jin;Terada, Tomohiro;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi