{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:17:30Z","timestamp":1791328650799,"version":"4.3.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>in vitro<\/jats:italic> experiments, insulin resistance was induced by applying tunicamycin to HUVECs. Uncarboxylated osteocalcin not only markedly reduced the phosphorylations of PERK and eIF2\u03b1, but also elevated the phosphorylations of IRS-1 and Akt, resulting in improvement of insulin signal transduction via PI3K\/Akt\/NF-\u03baB 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-\u03baB signaling in tunicamycin-induced HUVECs, suggesting osteocalcin as a potential treatment for the vascular complications of T2DM.<\/jats:p>","DOI":"10.1038\/s41598-017-00163-2","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T10:01:13Z","timestamp":1488189673000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Undercarboxylated osteocalcin reverts insulin resistance induced by endoplasmic reticulum stress in human umbilical vein endothelial cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Qinyue","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"163_CR1","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1152\/physrev.1989.69.3.990","volume":"69","author":"PV Hauschka","year":"1989","unstructured":"Hauschka, P. 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