Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jang HJ,Kokrashvili Z,Theodorakis MJ,Carlson OD,Kim BJ,Zhou J,Kim HH,Xu X,Chan SL,Juhaszova M,Bernier M,Mosinger B,Margolskee RF,Egan JMdoi
10.1073/pnas.0706890104subject
Has Abstractpub_date
2007-09-18 00:00:00pages
15069-74issue
38eissn
0027-8424issn
1091-6490pii
0706890104journal_volume
104pub_type
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