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

Hira, Tohru; Koga, Toshiki; Sasaki, Kazuyo; Hara, Hiroshi

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

Hira, Tohru; Koga, Toshiki; Sasaki, Kazuyo et al.

Biochemical and Biophysical Research Communications, 2017, 492(2), 161-165

Permalink : https://hdl.handle.net/2115/85112

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/85112
タイトル	Canagliflozin potentiates GLP-1 secretion and lowers the peak of GIP secretion in rats fed a high-fat high-sucrose diet
著者	Hira, Tohru ; Koga, Toshiki ; Sasaki, Kazuyo ; Hara, Hiroshi
e-Rad_Researcher 10396301 著者名 Hira, Tohru
著者名 Koga, Toshiki
著者名 Sasaki, Kazuyo
e-Rad_Researcher 70198894 著者名 Hara, Hiroshi
言語	英語
キーワード	Diet–induced obesity
	CanagliflozinGlucagon-like peptide-1
	Glucose-dependent insulinotropic polypeptide
	Sodium-glucose cotransporter 1(SGLT1)
	GLT2 inhibitor
発行日	2017
収録物名	Biochemical and Biophysical Research Communications
巻(号)	492(2)
ページ	161-165
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	(c) 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0006-291X
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.bbrc.2017.08.031