Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin
Background. Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity. Methods. Alizarin red staining was used to investigate the mineralization. Western bl...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3025538 |
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| _version_ | 1849695722499211264 |
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| author | Yafang Zhang Ling Li Yongze Zhang Sunjie Yan Lingning Huang |
| author_facet | Yafang Zhang Ling Li Yongze Zhang Sunjie Yan Lingning Huang |
| author_sort | Yafang Zhang |
| collection | DOAJ |
| description | Background. Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity. Methods. Alizarin red staining was used to investigate the mineralization. Western blotting and ELISA methods were used to measure protein expression. Immunofluorescence staining was used to investigate the protein nuclear transfer. Results. High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROE) significantly promoted the Runx2 and OCN expression. The increase of insulin, Gprc6a, and Glut2 by osteoblast culture medium overexpressing insulin receptor was reversed by osteocalcin neutralizing antibody. Undercarboxylated osteocalcin (ucOC) suppressed the lipotoxic islet β-cell damage caused by palmitic acid. The FOXO1 from intranuclear to extranuclear was also significantly increased after ucOC treatment compared with the group PA. Knockdown of Gprc6a or suppression of PI3K/AKT signal pathway could reverse the upregulation of GPRC6A/PI3K/AKT/FoxO1/Pdx1 caused by ucOC. Conclusion. OCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity. |
| format | Article |
| id | doaj-art-ce151a541bd74e868d4e8565aeb66bc1 |
| institution | DOAJ |
| issn | 2314-6753 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ce151a541bd74e868d4e8565aeb66bc12025-08-20T03:19:41ZengWileyJournal of Diabetes Research2314-67532022-01-01202210.1155/2022/3025538Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by OsteocalcinYafang Zhang0Ling Li1Yongze Zhang2Sunjie Yan3Lingning Huang4Department of EndocrinologyDepartment of EndocrinologyDepartment of EndocrinologyDepartment of EndocrinologyDepartment of EndocrinologyBackground. Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity. Methods. Alizarin red staining was used to investigate the mineralization. Western blotting and ELISA methods were used to measure protein expression. Immunofluorescence staining was used to investigate the protein nuclear transfer. Results. High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROE) significantly promoted the Runx2 and OCN expression. The increase of insulin, Gprc6a, and Glut2 by osteoblast culture medium overexpressing insulin receptor was reversed by osteocalcin neutralizing antibody. Undercarboxylated osteocalcin (ucOC) suppressed the lipotoxic islet β-cell damage caused by palmitic acid. The FOXO1 from intranuclear to extranuclear was also significantly increased after ucOC treatment compared with the group PA. Knockdown of Gprc6a or suppression of PI3K/AKT signal pathway could reverse the upregulation of GPRC6A/PI3K/AKT/FoxO1/Pdx1 caused by ucOC. Conclusion. OCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity.http://dx.doi.org/10.1155/2022/3025538 |
| spellingShingle | Yafang Zhang Ling Li Yongze Zhang Sunjie Yan Lingning Huang Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin Journal of Diabetes Research |
| title | Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin |
| title_full | Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin |
| title_fullStr | Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin |
| title_full_unstemmed | Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin |
| title_short | Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin |
| title_sort | improvement of lipotoxicity induced islet β cellular insulin secretion disorder by osteocalcin |
| url | http://dx.doi.org/10.1155/2022/3025538 |
| work_keys_str_mv | AT yafangzhang improvementoflipotoxicityinducedisletbcellularinsulinsecretiondisorderbyosteocalcin AT lingli improvementoflipotoxicityinducedisletbcellularinsulinsecretiondisorderbyosteocalcin AT yongzezhang improvementoflipotoxicityinducedisletbcellularinsulinsecretiondisorderbyosteocalcin AT sunjieyan improvementoflipotoxicityinducedisletbcellularinsulinsecretiondisorderbyosteocalcin AT lingninghuang improvementoflipotoxicityinducedisletbcellularinsulinsecretiondisorderbyosteocalcin |