T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1.
Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.
Margolskee
Robert F
RF
Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA. robert.margolskee@mssm.edu
Dyer
Jane
J
Kokrashvili
Zaza
Z
Salmon
Kieron S H
KS
Ilegems
Erwin
E
Daly
Kristian
K
Maillet
Emeline L
EL
Ninomiya
Yuzo
Y
Mosinger
Bedrich
B
Shirazi-Beechey
Soraya P
SP
D000818:Animals; D002478:Cells, Cultured; D019422:Dietary Sucrose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism*; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology
D019422:Dietary Sucrose; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D051269:Sodium-Glucose Transporter 1; D013549:Sweetening Agents; C431926:taste receptors, type 1; D013395:Sucrose; C026285:trichlorosucrose; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose