Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization

Kanda, Hajime; Tamori, Yoshikazu; Shinoda, Hiroaki; Yoshikawa, Mari; Sakaue, Motoyoshi; Udagawa, Jun; Otani, Hiroki; Tashiro, Fumi; Miyazaki, Jun-ichi; Kasuga, Masato

doi:info:doi/10.1172/JCI22681

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このアイテムへのリンクには次のURLをご利用ください:https://doi.org/10.1172/JCI22681

このアイテムへのリンクには次のURLをご利用ください:http://hdl.handle.net/11094/23118

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タイトル	Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization
著者	Kanda, Hajime Kanda, Hajime
	Tamori, Yoshikazu Tamori, Yoshikazu
	Shinoda, Hiroaki Shinoda, Hiroaki
	Yoshikawa, Mari Yoshikawa, Mari
	Sakaue, Motoyoshi Sakaue, Motoyoshi
	Udagawa, Jun Udagawa, Jun
	Otani, Hiroki Otani, Hiroki
	Tashiro, Fumi Tashiro, Fumi
	Miyazaki, Jun-ichi Miyazaki, Jun-ichi
	Kasuga, Masato Kasuga, Masato
抄録	Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the subsequent fusion of these vesicles with the plasma membrane, resulting in the externalization of GLUT4. Fusion of the GLUT4-containing vesicles with the plasma membrane is mediated by a soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex consisting of vesicle-associated membrane protein 2 (VAMP2), 23-kDa synaptosomal-associated protein (SNAP23), and syntaxin4. We have now generated mouse embryos deficient in the syntaxin4 binding protein Munc18c and show that the insulin-induced appearance of GLUT4 at the cell surface is enhanced in adipocytes derived from these Munc18c−/− mice compared with that in Munc18c+/+ cells. Wortmannin, an inhibitor of PI3K, inhibited insulin-stimulated GLUT4 externalization, without affecting GLUT4 translocation to the cell periphery, in Munc18c+/+ adipocytes, but it did not affect GLUT4 externalization in Munc18c−/− cells. Phosphatidylinositol 3-phosphate, which induced GLUT4 translocation to the cell periphery without externalization in Munc18c+/+ cells, elicited GLUT4 externalization in Munc18c−/− cells. These findings demonstrate that Munc18c inhibits insulin-stimulated externalization of GLUT4 in a wortmannin-sensitive manner, and they suggest that disruption of the interaction between syntaxin4 and Munc18c in adipocytes might result in enhancement of insulin-stimulated GLUT4 externalization.
公開者	American Society for Clinical Investigation
掲載誌名	Journal of Clinical Investigation
巻	115
号	2
開始ページ	291
終了ページ	301
刊行年月	2005-02
ISSN	00219738
NCID	AA00695520
DOI	info:doi/10.1172/JCI22681
URL	http://hdl.handle.net/11094/23118
権利情報	Copyright © 2005 American Society for Clinical Investigation
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Clinical Investigation.115(2) P.291-P.301
DC.title	Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization
DC.creator	Kanda, Hajime
	Tamori, Yoshikazu
	Shinoda, Hiroaki
	Yoshikawa, Mari
	Sakaue, Motoyoshi
	Udagawa, Jun
	Otani, Hiroki
	Tashiro, Fumi
	Miyazaki, Jun-ichi
	Kasuga, Masato
DC.publisher	American Society for Clinical Investigation
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2005-02
DC.identifier	info:doi/10.1172/JCI22681
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23118
DCTERMS.abstract	Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the subsequent fusion of these vesicles with the plasma membrane, resulting in the externalization of GLUT4. Fusion of the GLUT4-containing vesicles with the plasma membrane is mediated by a soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complex consisting of vesicle-associated membrane protein 2 (VAMP2), 23-kDa synaptosomal-associated protein (SNAP23), and syntaxin4. We have now generated mouse embryos deficient in the syntaxin4 binding protein Munc18c and show that the insulin-induced appearance of GLUT4 at the cell surface is enhanced in adipocytes derived from these Munc18c−/− mice compared with that in Munc18c+/+ cells. Wortmannin, an inhibitor of PI3K, inhibited insulin-stimulated GLUT4 externalization, without affecting GLUT4 translocation to the cell periphery, in Munc18c+/+ adipocytes, but it did not affect GLUT4 externalization in Munc18c−/− cells. Phosphatidylinositol 3-phosphate, which induced GLUT4 translocation to the cell periphery without externalization in Munc18c+/+ cells, elicited GLUT4 externalization in Munc18c−/− cells. These findings demonstrate that Munc18c inhibits insulin-stimulated externalization of GLUT4 in a wortmannin-sensitive manner, and they suggest that disruption of the interaction between syntaxin4 and Munc18c in adipocytes might result in enhancement of insulin-stimulated GLUT4 externalization.
DC.rights	Copyright © 2005 American Society for Clinical Investigation
citation_title	Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization
citation_author	Kanda, Hajime
	Tamori, Yoshikazu
	Shinoda, Hiroaki
	Yoshikawa, Mari
	Sakaue, Motoyoshi
	Udagawa, Jun
	Otani, Hiroki
	Tashiro, Fumi
	Miyazaki, Jun-ichi
	Kasuga, Masato
citation_publisher	American Society for Clinical Investigation
citation_language	英語
citation_date	2005-02
citation_journal_title	Journal of Clinical Investigation
citation_volume	115
citation_issue	2
citation_firstpage	291
citation_lastpage	301
citation_issn	00219738
citation_doi	info:doi/10.1172/JCI22681
citation_public_url	http://hdl.handle.net/11094/23118

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