Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells

Abstract Osteocalcin has been considered to be an important regulator of energy metabolism in type 2 diabetes mellitus (T2DM). However, the mechanism underlying the involvement of uncarboxylated osteocalcin in the vascular complications of T2DM is not fully understood. In the present study, we analy...

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Autores principales:	Qinyue Guo, Huixia Li, Lin Xu, Shufang Wu, Hongzhi Sun, Bo Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af08871ac69f4162837fbc7c955bf3a6
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spelling	oai:doaj.org-article:af08871ac69f4162837fbc7c955bf3a62021-12-02T11:52:42ZUndercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells10.1038/s41598-017-00163-22045-2322https://doaj.org/article/af08871ac69f4162837fbc7c955bf3a62017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00163-2https://doaj.org/toc/2045-2322Abstract Osteocalcin has been considered to be an important regulator of energy metabolism in type 2 diabetes mellitus (T2DM). However, the mechanism underlying the involvement of uncarboxylated osteocalcin in the vascular complications of T2DM is not fully understood. In the present study, we analyzed the potential correlations between uncarboxylated osteocalcin and macro- or microangiopathic complications in subjects with T2DM and tested the impact of uncarboxylated osteocalcin on insulin resistance in human umbilical vein endothelial cells (HUVECs). The results showed that the serum levels of uncarboxylated osteocalcin were lower in subjects with vascular complications of T2DM. Univariate correlation analyses revealed negative correlations between uncarboxylated osteocalcin and waist-to-hip ratio, HbA1c, and HOMA-IR. In in vitro experiments, insulin resistance was induced by applying tunicamycin to HUVECs. Uncarboxylated osteocalcin not only markedly reduced the phosphorylations of PERK and eIF2α, but also elevated the phosphorylations of IRS-1 and Akt, resulting in improvement of insulin signal transduction via PI3K/Akt/NF-κB signaling in HUVECs. Therefore, there is a possible relationship between uncarboxylated osteocalcin and the vascular complications of T2DM. Uncarboxylated osteocalcin partially improves insulin signal transduction via PI3K/Akt/NF-κB signaling in tunicamycin-induced HUVECs, suggesting osteocalcin as a potential treatment for the vascular complications of T2DM.Qinyue GuoHuixia LiLin XuShufang WuHongzhi SunBo ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qinyue Guo Huixia Li Lin Xu Shufang Wu Hongzhi Sun Bo Zhou Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
description	Abstract Osteocalcin has been considered to be an important regulator of energy metabolism in type 2 diabetes mellitus (T2DM). However, the mechanism underlying the involvement of uncarboxylated osteocalcin in the vascular complications of T2DM is not fully understood. In the present study, we analyzed the potential correlations between uncarboxylated osteocalcin and macro- or microangiopathic complications in subjects with T2DM and tested the impact of uncarboxylated osteocalcin on insulin resistance in human umbilical vein endothelial cells (HUVECs). The results showed that the serum levels of uncarboxylated osteocalcin were lower in subjects with vascular complications of T2DM. Univariate correlation analyses revealed negative correlations between uncarboxylated osteocalcin and waist-to-hip ratio, HbA1c, and HOMA-IR. In in vitro experiments, insulin resistance was induced by applying tunicamycin to HUVECs. Uncarboxylated osteocalcin not only markedly reduced the phosphorylations of PERK and eIF2α, but also elevated the phosphorylations of IRS-1 and Akt, resulting in improvement of insulin signal transduction via PI3K/Akt/NF-κB signaling in HUVECs. Therefore, there is a possible relationship between uncarboxylated osteocalcin and the vascular complications of T2DM. Uncarboxylated osteocalcin partially improves insulin signal transduction via PI3K/Akt/NF-κB signaling in tunicamycin-induced HUVECs, suggesting osteocalcin as a potential treatment for the vascular complications of T2DM.
format	article
author	Qinyue Guo Huixia Li Lin Xu Shufang Wu Hongzhi Sun Bo Zhou
author_facet	Qinyue Guo Huixia Li Lin Xu Shufang Wu Hongzhi Sun Bo Zhou
author_sort	Qinyue Guo
title	Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
title_short	Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
title_full	Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
title_fullStr	Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
title_full_unstemmed	Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
title_sort	undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/af08871ac69f4162837fbc7c955bf3a6
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Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells

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