Hirsh A J, Cheeseman C I
Membrane Transport Group, Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
J Biol Chem. 1998 Jun 5;273(23):14545-9. doi: 10.1074/jbc.273.23.14545.
The dual lumenaly and vascularly perfused small intestine was used to determine the mechanism by which cholecystokinin octapeptide (CCK-8) decreases the rate of glucose absorption. With CCK-8 in the vascular perfusate the rate of 3-O-methyl-D-glucose absorption decreased, whereas the rate of D-fructose absorption was unaffected. The substrate pool size within the tissue during steady-state transport, in the presence and absence of CCK-8, was estimated by compartmental analysis of the 3-O-methyl-D-glucose washout into the vascular bed. When CCK-8 was included in the vascular perfusate, the absorptive cell pool size decreased when compared with untreated tissue. Both the steady-state hexose absorption data and the washout studies indicated that the locus of action of CCK-8 was the SGLT1 transporter located in the brush-border membrane. The SGLT1 protein abundance in isolated brush-border membranes, as quantified by Western blotting, showed a decrease that paralleled the decrease in the steady-state transport rate induced by CCK-8. These results indicate that CCK-8 diminishes the rate of intestinal hexose absorption by decreasing SGLT1 protein abundance in the brush-border membrane of the rat jejunum and therefore provides evidence for acute enteric hormonal regulation of the rate of glucose absorption across the small intestine.
采用双腔和血管灌注的小肠来确定八肽胆囊收缩素（CCK-8）降低葡萄糖吸收速率的机制。当血管灌注液中存在CCK-8时，3-O-甲基-D-葡萄糖的吸收速率降低，而D-果糖的吸收速率未受影响。在存在和不存在CCK-8的情况下，通过对3-O-甲基-D-葡萄糖向血管床的洗脱进行房室分析，估计稳态转运期间组织内的底物池大小。当血管灌注液中包含CCK-8时，与未处理的组织相比，吸收细胞池大小减小。稳态己糖吸收数据和洗脱研究均表明，CCK-8的作用位点是位于刷状缘膜的SGLT1转运体。通过蛋白质印迹法定量的分离刷状缘膜中SGLT1蛋白丰度显示出下降，这与CCK-8诱导的稳态转运速率下降平行。这些结果表明，CCK-8通过降低大鼠空肠刷状缘膜中SGLT1蛋白丰度来降低肠道己糖吸收速率，因此为小肠葡萄糖吸收速率的急性肠内分泌调节提供了证据。
