Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.
Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.
Jang
Hyeung-Jin
HJ
National Institute on Aging/National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Kokrashvili
Zaza
Z
Theodorakis
Michael J
MJ
Carlson
Olga D
OD
Kim
Byung-Joon
BJ
Zhou
Jie
J
Kim
Hyeon Ho
HH
Xu
Xiangru
X
Chan
Sic L
SL
Juhaszova
Magdalena
M
Bernier
Michel
M
Mosinger
Bedrich
B
Margolskee
Robert F
RF
Egan
Josephine M
JM
D000818:Animals; D002478:Cells, Cultured; D004386:Duodenum / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D052216:Glucagon-Like Peptide 1; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose