Sugar sensor genes in the murine gastrointestinal tract display a cephalocaudal axis of expression and a diurnal rhythm

Abstract

Distributed along the length of the gastrointestinal (GI) tract are nutrient sensing cells that release numerous signaling peptides influencing GI function, nutrient homeostasis and energy balance. Recent studies have shown a diurnal rhythm in GI nutrient sensing, but the mechanisms responsible for rhythmicity are poorly understood. In this report we studied murine GI sugar sensor gene and protein expression levels in the morning (7 AM) and evening (7 PM). Sweet taste receptor ( tas1r2/tas1r3/gnat3/gnat1) sugar transporter ( slc5a1, slc2a2, slc2a5) and putative sugar sensor ( slc5a4a and slc5a4b) gene expression levels were highest in tongue and proximal and distal small intestine, respectively. Clock gene ( cry2/arntl) activity was detected in all regions studied. Slc5a4a and slc5a4b gene expression showed clear diurnal rhythmicity in the small intestine and stomach, respectively, although no rhythmicity was detected in SGLT3 protein expression. Tas1r2, tas1r3, gnat1, and gcg displayed a limited rhythm in gene expression in proximal small intestine. Microarray analysis revealed a diurnal rhythm in gut peptide gene expression in tongue (7 AM vs. 7 PM) and in silico promoter analysis indicated intestinal sugar sensors and transporters possessed the canonical E box elements necessary for clock gene control over gene transcription. In this report we present evidence of a diurnal rhythm in genes that are responsible for intestinal nutrient sensing that is most likely controlled by clock gene activity. Disturbances in clock gene/nutrient sensing interactions may be important in the development of diet-related diseases, such as obesity and diabetes.