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Canagliflozin potentiates GLP-1 secretion and lowers the peak of GIP secretion in rats fed a high-fat high-sucrose diet

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Title: Canagliflozin potentiates GLP-1 secretion and lowers the peak of GIP secretion in rats fed a high-fat high-sucrose diet
Authors: Hira, Tohru Browse this author →KAKEN DB
Koga, Toshiki Browse this author
Sasaki, Kazuyo Browse this author
Hara, Hiroshi Browse this author →KAKEN DB
Keywords: Diet–induced obesity
CanagliflozinGlucagon-like peptide-1
Glucose-dependent insulinotropic polypeptide
Sodium-glucose cotransporter 1(SGLT1)
GLT2 inhibitor
Issue Date: 2017
Journal Title: Biochemical and Biophysical Research Communications
Volume: 492
Issue: 2
Start Page: 161
End Page: 165
Publisher DOI: 10.1016/j.bbrc.2017.08.031
Abstract: The glucose-induced secretion of incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), is dependent on luminal glucose levels and transport of glucose via the sodium-glucose transporter 1 (SGLT1) in the small intestine. Because GLP-1 and GIP function in decreasing and increasing the body weight, respectively, we aimed to analyze the effect of transient inhibition of SGLT1 by canagliflozin on incretin secretion in an obese rat model. Male Sprague-Dawley rats were maintained on a high-fat high-sucrose diet for 6?7 weeks, and plasma GLP-1 and GIP levels were measured during an oral glucose tolerance test (OGTT). In addition, GLP-1 secretion was examined in a murine GLP-1 producing enteroendocrine cell line, GLUTag. Concomitant administration of 10 mg/kg canagliflozin with glucose loading suppressed glucose excursion, increased total GLP-1 levels, and reduced total GIP levels in systemic circulation, as revealed in the OGTT. Total and active GLP-1 levels were increased in portal blood, whereas total and active GIP levels tended to be decreased 15 min after the administration of canagliflozin with glucose. Canagliflozin (at 0.1?30 μM) did not directly affect release of GLP-1 in vitro. These results suggest that the oral administration of canagliflozin suppresses GIP secretion via the inhibition of SGLT1 in the upper part of the intestine and enhances GLP-1 secretion by increasing the glucose delivery to the lower part of the small intestine in an obese rodent model.
Rights: (c) 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:農学院・農学研究院 (Graduate School of Agriculture / Faculty of Agriculture) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 比良 徹

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