Secretion of GLP-1 but not GIP is potently stimulated by luminal D-Allulose (D-Psicose) in rats

Jul 10, 2026

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Glucagon-like peptide 1 (GLP-1), a gut incretin hormone, is secreted in response to luminal nutrients such as glucose and fructose. D-Allulose (D-psicose), a rare C-3 epimer of D-fructose with reported anti-diabetic/anti-obese effects, was tested for its ability to stimulate GLP-1 secretion. Oral, but not intraperitoneal, allulose increased plasma GLP-1 in a dose-dependent manner and raised total and active GLP-1 in portal blood without changing GIP. Luminal duodenal/ileal administration enhanced portal GLP-1, and the response was blocked by xanthohumol, indicating a glucose/fructose transport-dependent mechanism.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages6

Reading Time15 min

Introduction

Materials and methods

Materials

Animals and measurement of plasma gut hormones

Biochemical and Biophysical Research Communications 496 (2018) 898e903 Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal [homepage: www. elsevier. com/locate/ybbrc](homepage: www. elsevier. com/locate/ybbrc) | Secretion of GLP-1 but not GIP is potently stimulated by luminal DAllulose (D-Psicose) in rats Masaki Hayakawa a, Tohru Hira a, b, *, Masako Nakamura c, Tetsuo Iida c, Yuka Kishimoto c, Hiroshi Hara a, b a Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan b Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan c Research & Devlopment, Matsutani Chemical Industry Co., Ltd., 5-3, Kita-Itami, Itami 664-8508, Japan | | | | | --- | --- | --- | --- | | a r t i c l e i n f o | | a b s t r a c t | | | Article history: Received 17 January 2018 Accepted 19 January 2018 | | Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. D-Allulose (allulose), also known as D-psicose, is a C-3 isomer of D-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0.5e2.0 g/kg body weight) elevated plasma GLP-1 levels for more than 2 h in a dose-dependent manner. The effects of allulose on GLP-1 secretion were higher than that of dextrin, fructose, or glucose. In addition, oral allulose increased total and active GLP-1, but not glucosedependent insulinotropic polypeptide (GIP), levels in the portal vein. In anesthetized rats equipped with a portal catheter, luminal (duodenum and ileum) administration of allulose increased portal GLP-1 levels, indicating the luminal effect of allulose. Allulose-induced GLP-1 secretion was abolished in the presence of xanthohumol (a glucose/fructose transport inhibitor), but not in the presence of inhibitors of the sodium-dependent glucose cotransporter 1 or the sweet taste receptor. These results demonstrate a potent and lasting effect of orally administered allulose on GLP-1 secretion in rats, without affecting GIP secretion. The potent and selective GLP-1-releasing effect of allulose holds promise for the prevention and treatment of glucose intolerance through promoting endogenous GLP-1 secretion. © 2018 Elsevier Inc. All rights reserved. | | | Keywords: GLP-1 GIPAllulose | | | | 1. Introduction Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal hormones called incretins that have insulinotropic effects [1], and incretin mimeticsand enhancers have been used to treat type-2 diabetes. Secretion of GLP-1 and GIP is stimulated by luminal nutrients, and the mechanisms involved have been recently unveiled. However, attempts for prevention and treatment of glucose intolerance through stimulated production and/or release of endogenous GLP-1 have not Abbreviations: GLP-1, glucagon-like peptide-1; GIP, Glucose-dependent insulinotropic polypeptide; Allulose, D-Allulose; GLUT5, glucose transporter 5; SGLT, sodiumedependent glucose cotransporter. * Corresponding author. Laboratory of Nutritional Biochemistry, Research Faculty of Agriculture, Hokkaido University, Kita-9, Nishi-9, Kita-ku, Sapporo 060-8589, Japan. E-mail address: [hira@chem.agr.hokudai.ac.jp](hira@chem.agr.hokudai.ac.jp) (T. Hira). [https://doi.org/10.1016/j.bbrc.2018.01.128](https://doi.org/10.1016/j.bbrc.2018.01.128) 0006-291X/© 2018 Elsevier Inc. All rights reserved. been successful. Prevention and treatment of diabetes have also been attempted using “rare sugars”, which are deﬁned as monosaccharides and their derivatives that are present in limited quantities in nature [2]. D-Allulose

FAQs

How does oral D-allulose affect GLP-1 secretion compared with intraperitoneal administration in rats?

Oral D-allulose increases plasma GLP-1 levels for more than 2 hours in a dose-dependent manner, whereas intraperitoneal administration does not show the same elevation.

Does D-allulose influence both GLP-1 and GIP secretion?

D-allulose increases total and active GLP-1 levels in portal blood but does not affect glucosedependent insulinotropic polypeptide (GIP) levels.

What evidence supports a luminal site of action for allulose-induced GLP-1 secretion?

In anesthetized rats with a portal catheter, administering allulose into the duodenum and ileum raises portal GLP-1 levels, indicating that luminal exposure triggers the effect.

Jul 10, 2026

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