Circadian Periodicity of Intestinal Na+/Glucose Cotransporter 1 mRNA Levels Is Transcriptionally Regulated

Abstract

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-1alpha was present in complexes throughout the day, while HNF-1beta 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.