Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Okita, Tomonori; Kita, Shunbun; Fukuda, Shiro; Kondo, Yuta; Sakaue, Taka-aki; Iioka, Masahito; Fukuoka, Keita; Kawada, Keitaro; Nagao, Hirofumi; Obata, Yoshinari; Fujishima, Yuya; Ebihara, Takeshi; Matsumoto, Hisatake; Nakagawa, Satoshi; Kimura, Tadashi; Nishizawa, Hitoshi; Shimomura, Iichiro

doi:https://doi.org/10.1016/j.bbrc.2024.150403

Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Okita, Tomonori; Kita, Shunbun; Fukuda, Shiro et al.

Biochemical and Biophysical Research Communications, 2024, 732, 150403

Number of Access:2,164（2025-07-18 10:22 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98166

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Title	Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling
Creator	CreatorName Okita, Tomonori
	NRID 1000010746572 1000010746572 ORCID 0000-0002-8937-0053 0000-0002-8937-0053 researchmap permalink Shunbun_Kita Shunbun_Kita Scopus Author ID 36873116500 36873116500 CreatorName Kita, Shunbun
	NRID 1000000896467 1000000896467 researchmap permalink sfukuda-ou sfukuda-ou Scopus Author ID 55766129200 55766129200 CreatorName Fukuda, Shiro
	CreatorName Kondo, Yuta
	CreatorName Sakaue, Taka-aki
	CreatorName Iioka, Masahito
	CreatorName Fukuoka, Keita
	CreatorName Kawada, Keitaro
	NRID 1000070983146 1000070983146 ORCID 0009-0001-1261-4160 0009-0001-1261-4160 researchmap permalink Hirofumi_Nagao Hirofumi_Nagao CreatorName Nagao, Hirofumi
	researchmap permalink osaka-u-obata osaka-u-obata ORCID 0000-0002-3443-3635 0000-0002-3443-3635 CreatorName Obata, Yoshinari
	NRID 1000010779789 1000010779789 researchmap permalink Yuya_Fujishima Yuya_Fujishima Scopus Author ID 54410318600 54410318600 CreatorName Fujishima, Yuya
	NRID 1000010813975 1000010813975 ORCID 0000-0003-4101-0419 0000-0003-4101-0419 researchmap permalink ebihara830 ebihara830 CreatorName Ebihara, Takeshi
	NRID 1000070644003 1000070644003 researchmap permalink 38283828 38283828 Scopus Author ID 36632584800 36632584800 CreatorName Matsumoto, Hisatake
	NRID 1000030650593 1000030650593 ORCID 0000-0001-6540-9040 0000-0001-6540-9040 researchmap permalink snakagawa snakagawa Scopus Author ID 56514567200 56514567200 CreatorName Nakagawa, Satoshi
	NRID 1000090240845 1000090240845 researchmap permalink read0106368 read0106368 Scopus Author ID 35421281200 35421281200 CreatorName Kimura, Tadashi
	NRID 1000020379259 1000020379259 researchmap permalink Hitoshi_Nishizawa Hitoshi_Nishizawa Scopus Author ID 7102282682 7102282682 CreatorName Nishizawa, Hitoshi
	NRID 1000060346145 1000060346145 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 CreatorName Shimomura, Iichiro
Subject	Endothelial cells
	Insulin demand
	Insulin signalling
	soluble T-cadherin
Description	Okita T., Kita S., Fukuda S., et al. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochemical and Biophysical Research Communications 732, 150403 (2024); https://doi.org/10.1016/j.bbrc.2024.150403.
Abstract	Aim and objective: Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear. Methods and results: Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling. Conclusion: We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling.
Publisher	Elsevier B.V.
Source Title	Biochemical and Biophysical Research Communications
Volume (Issue)	732
Page	150403
Date of Issued	2024-11-05
Language	English
Handle URL	https://hdl.handle.net/11094/98166
PISSN	0006291X
eISSN	10902104
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.bbrc.2024.150403
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Biochemical and Biophysical Research Communications. 2024, 732, p. 150403
DC.title	Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling
DC.creator	Okita, Tomonori
	Kita, Shunbun
	Fukuda, Shiro
	Kondo, Yuta
	Sakaue, Taka-aki
	Iioka, Masahito
	Fukuoka, Keita
	Kawada, Keitaro
	Nagao, Hirofumi
	Obata, Yoshinari
	Fujishima, Yuya
	Ebihara, Takeshi
	Matsumoto, Hisatake
	Nakagawa, Satoshi
	Kimura, Tadashi
	Nishizawa, Hitoshi
	Shimomura, Iichiro
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-11-05
DC.identifier	https://doi.org/10.1016/j.bbrc.2024.150403
DC.subject	Endothelial cells
	Insulin demand
	Insulin signalling
	soluble T-cadherin
DC.description	Okita T., Kita S., Fukuda S., et al. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochemical and Biophysical Research Communications 732, 150403 (2024); https://doi.org/10.1016/j.bbrc.2024.150403.
DCTERMS.abstract	Aim and objective: Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear. Methods and results: Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling. Conclusion: We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	98166
citation_title	Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling
citation_author	Okita, Tomonori
	Kita, Shunbun
	Fukuda, Shiro
	Kondo, Yuta
	Sakaue, Taka-aki
	Iioka, Masahito
	Fukuoka, Keita
	Kawada, Keitaro
	Nagao, Hirofumi
	Obata, Yoshinari
	Fujishima, Yuya
	Ebihara, Takeshi
	Matsumoto, Hisatake
	Nakagawa, Satoshi
	Kimura, Tadashi
	Nishizawa, Hitoshi
	Shimomura, Iichiro
citation_publisher	Elsevier B.V.
citation_language	English
citation_date	2024-11-05
citation_journal_title	Biochemical and Biophysical Research Communications
citation_volume	732
citation_firstpage	150403
citation_doi	https://doi.org/10.1016/j.bbrc.2024.150403
citation_public_url	https://hdl.handle.net/11094/98166

Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

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