Region-dependent role of the mucous/glycocalyx layers in insulin permeation across rat small intestinal membrane
Region-dependent role of the mucous/glycocalyx layers in insulin permeation across rat small intestinal membrane
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DOI：
10.1007/s11095-005-6137-z
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发表时间：
2005-11-01
影响因子：
3.7
通讯作者：
Takayama, K
中科院分区：
文献类型：
--
作者：
Aoki, Y;Morishita, M;Takayama, K
通过体外研究，研究了大鼠小肠粘膜/糖萼层作为扩散或酶屏障对胰岛素吸收的贡献的区域差异。通过将大鼠十二指肠、空肠和回肠的粘液/糖萼层原位暴露于透明质酸酶溶液中，成功去除了这些粘液/糖萼层，而不损害膜的完整性。在体外转运实验中，与PBS预处理（对照）组相比，透明质酸酶预处理组的胰岛素表观渗透系数（P-app）在所有小肠区域均显著增加，PBS和透明质酸酶预处理组中胰岛素的P-app均按以下顺序增加：十二指肠<空肠<回肠。另一方面，不考虑小肠区域，FD-4和安替比林的P-app（分别为被动的细胞帕拉和跨细胞渗透标记物）在PBS和透明质酸酶预处理组之间没有表现出显著差异。此外，透明质酸酶预处理去除的粘液/糖萼层中有大量胰岛素降解，且粘液/糖萼层中的降解活性表现出以下区域差异：十二指肠>空肠>回肠。这些发现表明，无论小肠区域如何，粘液/糖萼层主要作为酶屏障而不是扩散屏障促进胰岛素渗透。此外，粘液/糖萼层和刷状缘膜中酶活性的变化是胰岛素转运区域差异的一个因素。
The regional difference in the contribution of the mucous/glycocalyx layers in rat small intestine, as a diffusional or enzymatic barrier, to the absorption of insulin was investigated by in vitro studies. The mucous/glycocalyx layers from the duodenum, the jejunum, and the ileum in rat were successfully removed without damaging membrane integrity, by exposing them to a hyaluronidase solution in situ. In an in vitro transport experiment, the apparent permeability coefficient (P-app) of insulin for the hyaluronidase-pretreated group was significantly increased compared to the PBS-pretreated (control) group in all small intestinal regions, and the P-app of insulin in both PBS- and hyaluronidase-pretreated groups increased in the following order: duodenum < jejunum < ileum. On the other hand, irrespective of small intestinal regions, the P-app of FD-4 and of antipyrine, respectively the passive para- and transcellular permeation marker, exhibited no significant differences between PBS- and hyaluronidase-pretreated group. In addition, a significant amount of insulin was degraded in the mucous/glycocalyx layers compartment removed by hyaluronidase pretreatment, and the degradation activity in the mucous/glycocalyx layers showed regional differences in the following order: duodenum > jejunum > ileum. These findings suggest that, irrespective of small intestinal regions, the mucous/glycocalyx layers contributed to insulin permeation predominantly as an enzymatic barrier, and not as a diffusional barrier. Furthermore, the variation of the enzymatic activities in the mucous/glycocalyx layers and in the brush-border membrane would be one factor that accounts for the regional differences in the transport of insulin.