GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose

Yusaku Iwasaki, Mio Sendo, Katsuya Dezaki, Tohru Hira, Takehiro Sato, Masanori Nakata, Chayon Goswami, Ryohei Aoki, Takeshi Arai, Parmila Kumari, Masaki Hayakawa, Chiaki Masuda, Takashi Okada, Hiroshi Hara, Daniel J. Drucker, Yuichiro Yamada, Masaaki Tokuda and Toshihiko Yada ()
Additional contact information
Yusaku Iwasaki: Jichi Medical University School of Medicine
Mio Sendo: Jichi Medical University School of Medicine
Katsuya Dezaki: Jichi Medical University School of Medicine
Tohru Hira: Hokkaido University
Takehiro Sato: Akita University Graduate School of Medicine
Masanori Nakata: Jichi Medical University School of Medicine
Chayon Goswami: Jichi Medical University School of Medicine
Ryohei Aoki: Jichi Medical University School of Medicine
Takeshi Arai: Jichi Medical University School of Medicine
Parmila Kumari: Jichi Medical University School of Medicine
Masaki Hayakawa: Hokkaido University
Chiaki Masuda: Nippon Medical School
Takashi Okada: Nippon Medical School
Hiroshi Hara: Hokkaido University
Daniel J. Drucker: Lunenfeld Tanenbaum Research Institute, Mt. Sinai Hospital
Yuichiro Yamada: Akita University Graduate School of Medicine
Masaaki Tokuda: Kagawa University
Toshihiko Yada: Jichi Medical University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-017-02488-y

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