PMID- 28246389
OWN - NLM
STAT- MEDLINE
DCOM- 20190206
LR  - 20221207
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Mar 3
TI  - Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic 
      reticulum stress in human umbilical vein endothelial cells.
PG  - 46
LID - 10.1038/s41598-017-00163-2 [doi]
LID - 46
AB  - 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 eIF2alpha, but 
      also elevated the phosphorylations of IRS-1 and Akt, resulting in improvement of 
      insulin signal transduction via PI3K/Akt/NF-kappaB 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-kappaB signaling in tunicamycin-induced 
      HUVECs, suggesting osteocalcin as a potential treatment for the vascular 
      complications of T2DM.
FAU - Guo, Qinyue
AU  - Guo Q
AD  - Department of Respiratory and Critical Care Medicine, the First Affiliated 
      Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 
      710061, China.
FAU - Li, Huixia
AU  - Li H
AD  - Key Laboratory of Environment and Genes Related to Diseases, Medical School of 
      Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
FAU - Xu, Lin
AU  - Xu L
AD  - Department of Endocrinology, the Affiliated Guangren Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi, 710004, China.
FAU - Wu, Shufang
AU  - Wu S
AD  - Center for Translational Medicine, the First Affiliated Hospital of Xi'an 
      Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi, 710061, China.
FAU - Sun, Hongzhi
AU  - Sun H
AD  - Key Laboratory of Environment and Genes Related to Diseases, Medical School of 
      Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
FAU - Zhou, Bo
AU  - Zhou B
AD  - Department of Respiratory and Critical Care Medicine, the First Affiliated 
      Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 
      710061, China. zb_bob@stu.xjtu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170303
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 104982-03-8 (Osteocalcin)
RN  - 11089-65-9 (Tunicamycin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Diabetes Mellitus, Type 2/complications/drug therapy/*metabolism
MH  - Diabetic Angiopathies/drug therapy/etiology/metabolism
MH  - Endoplasmic Reticulum Stress
MH  - Glycated Hemoglobin/metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Osteocalcin/*metabolism/therapeutic use
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Tunicamycin/pharmacology
PMC - PMC5427815
COIS- The authors declare no competing financial interests.
EDAT- 2017/03/02 06:00
MHDA- 2019/02/07 06:00
PMCR- 2017/03/03
CRDT- 2017/03/02 06:00
PHST- 2016/09/21 00:00 [received]
PHST- 2017/02/09 00:00 [accepted]
PHST- 2017/03/02 06:00 [entrez]
PHST- 2017/03/02 06:00 [pubmed]
PHST- 2019/02/07 06:00 [medline]
PHST- 2017/03/03 00:00 [pmc-release]
AID - 10.1038/s41598-017-00163-2 [pii]
AID - 163 [pii]
AID - 10.1038/s41598-017-00163-2 [doi]
PST - epublish
SO  - Sci Rep. 2017 Mar 3;7(1):46. doi: 10.1038/s41598-017-00163-2.