GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose.
Iwasaki Yusaku, Sendo Mio, Dezaki Katsuya, Hira Tohru, Sato Takehiro, Nakata Masanori, Goswami Chayon, Aoki Ryohei, Arai Takeshi, Kumari Parmila, Hayakawa Masaki, Masuda Chiaki, Okada Takashi, Hara Hiroshi, Drucker Daniel J, Yamada Yuichiro, Tokuda Masaaki, Yada Toshihiko
Nature communications · 2018 · PMID 29317623 · 인용 196
Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models.
Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify D-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia.
Furthermore, when administered in a time-specific manner, chronic D-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.