Diurnal rhythmicity in intestinal SGLT-1 function, V(max), and mRNA expression topography.
Mechanisms underlying the circadian rhythmicity in intestinal sugar absorption remain unclear. To test whether this rhythmicity is caused by changes in Na(+)-glucose cotransporter 1 (SGLT-1) function, we measured phloridzin-inhibitable sugar fluxes as an index of SGLT-1 activity. Jejunum obtained from rats killed at 6-h intervals during a 12-h light-dark cycle (CT0 is circadian time 0 h, time of light onset) were mounted in Ussing chambers, and 3-O-methylglucose (3-OMG) fluxes were calculated before and after addition of phloridzin. 3-OMG-induced change in short-circuit current and absorptive flux were significantly greater at CT9 than at CT3. This increase was phloridzin inhibitable. Kinetic studies indicated a significant increase in SGLT-1 maximal velocity (V(max)) at CT9. Food intake between CT3 and CT9 was <10% of the daily total, indicating that the increased SGLT-1 activity was anticipatory. Diurnicity of SGLT-1 mRNA was confirmed by Northern blotting. Expression topography analyzed by in situ hybridization revealed more intense labeling along the entire villus axis at CT9 and CT15 compared with CT3 and CT21. We conclude that diurnicity in intestinal sugar absorption is caused by periodicity in SGLT-1 V(max).
Tavakkolizadeh
A
A
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Berger
U V
UV
Shen
K R
KR
Levitsky
L L
LL
Zinner
M J
MJ
Hediger
M A
MA
Ashley
S W
SW
Whang
E E
EE
Rhoads
D B
DB
D000818:Animals; D002940:Circadian Rhythm; D004435:Eating / Q000187:drug effects; D004553:Electric Conductivity; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000502:physiology*; D010695:Phlorhizin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1; D013997:Time Factors
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C037626:3'-O-methylguanosine; D006151:Guanosine; D010695:Phlorhizin