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.

Details

Title
GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose
Author
Iwasaki, Yusaku 1 ; Sendo, Mio 1 ; Dezaki, Katsuya 1 ; Hira, Tohru 2 ; Sato, Takehiro 3 ; Nakata, Masanori 1 ; Goswami, Chayon 1 ; Aoki, Ryohei 1 ; Arai, Takeshi 1 ; Kumari, Parmila 1 ; Hayakawa, Masaki 4 ; Masuda, Chiaki 5 ; Okada, Takashi 5 ; Hara, Hiroshi 2 ; Drucker, Daniel J 6 ; Yamada, Yuichiro 3 ; Tokuda, Masaaki 7 ; Yada, Toshihiko 8 

1  Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan 
2  Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan 
3  Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan 
4  Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan 
5  Department of Biochemistry and Molecular Biology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan 
6  Lunenfeld Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON, Canada 
7  Faculty of Medicine, Department of Cell Physiology, Kagawa University, Kita-gun, Kagawa, Japan 
8  Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan; Kansai Electric Power Medical Research Institute, Chuou-ku, Kobe, Japan 
First page
1
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-02488-y
ProQuest document ID
1986205579
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.