l-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels

Autor: Ida Marie Modvig, Mark M. Smits, Katrine Douglas Galsgaard, Anna Pii Hjørne, Anna Katarzyna Drzazga, Mette Marie Rosenkilde, Jens Juul Holst
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nutrition & Diabetes, Vol 14, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 2044-4052
DOI: 10.1038/s41387-024-00303-4
Popis: Abstract Background We previously reported that, among all the naturally occurring amino acids, l-valine is the most powerful luminal stimulator of glucagon-like peptide 1 (GLP-1) release from the upper part of the rat small intestine. This makes l-valine an interesting target for nutritional-based modulation of GLP-1 secretion. However, the molecular mechanism of l-valine-induced secretion remains unknown. Methods We aimed to investigate the effect of orally given l-valine in mice and to identify the molecular details of l-valine stimulated GLP-1 release using the isolated perfused rat small intestine and GLUTag cells. In addition, the effect of l-valine on hormone secretion from the distal intestine was investigated using a perfused rat colon. Results Orally given l-valine (1 g/kg) increased plasma levels of active GLP-1 comparably to orally given glucose (2 g/kg) in male mice, supporting that l-valine is a powerful stimulator of GLP-1 release in vivo (P > 0.05). Luminal l-valine (50 mM) strongly stimulated GLP-1 release from the perfused rat small intestine (P 0.05), suggesting that co-transport of l-valine and Na+ is not important for the depolarization necessary to activate the voltage-gated Ca2+-channels. Administration of the KATP-channel opener diazoxide (250 μM) completely blocked the l-valine induced GLP-1 response (P
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