title: 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 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.
authors.affiliation: 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.
authors.forename: Qinyue
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the Affiliated Guangren Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, Shaanxi, 710061, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006442:Glycated Hemoglobin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D015675:Osteocalcin / Q000378:metabolism* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D006442:Glycated Hemoglobin; D015675:Osteocalcin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014415:Tunicamycin; C517652:hemoglobin A1c protein, human