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J Biol Chem, Vol. 273, Issue 16, 9510-9516, April 17, 1998
From the Pediatric Endocrine Unit, Massachusetts General Hospital,
Laboratory of Tumor Biology, Massachusetts General Hospital Cancer
Center and Departments of Medicine and Pediatrics, Harvard Medical
School, Boston, Massachusetts 02114
Intestinal expression of the high affinity
Na+/glucose cotransporter 1 (SGLT1), which absorbs
dietary glucose and galactose, exhibits both circadian periodicity in
its activity and induction by dietary carbohydrate. Because the daily
variation in SGLT1 activity is established by the feeding schedule
(whether ad libitum or imposed) and persists in the absence
of food, this variation has been described as anticipatory. To
delineate the mechanisms regulating SGLT1, its expression was examined
in rats maintained in a 12-h photoperiod with free access to chow.
SGLT1 mRNA levels varied significantly, with the maximum abundance
occurring near the onset of dark and the minimum near the onset of
light. The SGLT1 transcription rate was 7-fold higher in the morning
(1000-1100 h) than in the afternoon (1600-1700 h). An element for
hepatocyte nuclear factor 1 (HNF-1) was identified in the SGLT1
promoter that formed different complexes with small intestinal nuclear extracts, depending on the time when the source animal was killed. Serological tests indicated that HNF-1
Circadian Periodicity of Intestinal Na+/Glucose
Cotransporter 1 mRNA Levels Is Transcriptionally Regulated
was present in complexes throughout the day, while HNF-1
binding exhibited circadian
periodicity. We propose that exchange of HNF-1 dimerization partners
contributes to circadian changes in SGLT1 transcription. Because SGLT1
mRNA levels also varied in rhesus monkeys (offset by approximately one-half day from rats), a similar mechanism appears to be present in
primates.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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