CHOLECYSTOKININ DECREASES INTESTINAL HEXOSE ABSORPTION BY A PARALLEL REDUCTION IN SGLT1 ABUNDANCE IN THE BRUSH-BORDER MEMBRANE

The dual lumenaly and vascularly perfused small intestine was used to determine the mechanism by which cholecystokinin octapeptide (CCK-8) d ecreases the rate of glucose absorption. With CCK-8 in the vascular pe rfusate 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 incl uded in the vascular perfusate, the absorptive cell pool size decrease d when compared with untreated tissue. Both the steady-state hexose ab sorption data and the washout studies indicated that the locus of acti on of CCK-8 was the SGLT1 transporter located in the brush-border memb rane. The SGLT1 protein abundance in isolated brush-border membranes, as quantified by Western blotting, showed a decrease that paralleled t he 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 m embrane of the rat jejunum and therefore provides evidence for acute e nteric hormonal regulation of the rate of glucose absorption across th e small intestine.