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) 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.
Hirsh
A J
AJ
Membrane Transport Group, Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Cheeseman
C I
CI
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D005632:Fructose / Q000493:pharmacokinetics; D005947:Glucose / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006601:Hexoses / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects* / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology*; D051269:Sodium-Glucose Transporter 1
D006601:Hexoses; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D005632:Fructose; D002766:Cholecystokinin; D005947:Glucose; D012844:Sincalide