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

Author

Listed:
  • 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
    Kansai Electric Power Medical Research Institute)

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.

Suggested Citation

  • 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 Ok, 2018. "GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02488-y
    DOI: 10.1038/s41467-017-02488-y
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