SH2B1 in beta-Cells Regulates Glucose Metabolism by Promoting beta-Cell Survival and Islet Expansion
文献类型：期刊论文
| 作者 | Chen, Zheng; Morris, David L.; Jiang, Lin; Liu, Yong（刘勇） ; Rui, Liangyou
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| 刊名 | DIABETES
 |
| 出版日期 | 2014 |
| 卷号 | 63期号:2页码:585-595 |
| 通讯作者 | Rui, LY (reprint author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. |
| 英文摘要 | IGF-1 and insulin promote -cell expansion by inhibiting -cell death and stimulating -cell proliferation, and the phosphatidylinositol (PI) 3-kinase/Akt pathway mediates insulin and IGF-1 action. Impaired -cell expansion is a risk factor for type 2 diabetes. Here, we identified SH2B1, which is highly expressed in -cells, as a novel regulator of -cell expansion. Silencing of SH2B1 in INS-1 832/13 -cells attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin (STZ)-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. Activation of the PI 3-kinase/Akt pathway in -cells was impaired in pancreas-specific SH2B1 knockout (PKO) mice fed a high-fat diet (HFD). HFD-fed PKO mice also had increased -cell apoptosis, decreased -cell proliferation, decreased -cell mass, decreased pancreatic insulin content, impaired insulin secretion, and exacerbated glucose intolerance. Furthermore, PKO mice were more susceptible to STZ-induced -cell destruction, insulin deficiency, and hyperglycemia. These data indicate that SH2B1 in -cells is an important prosurvival and proproliferative protein and promotes compensatory -cell expansion in the insulin-resistant state and in response to beta-cell stress. |
| 类目[WOS] | Endocrinology & Metabolism |
| 研究领域[WOS] | Endocrinology & Metabolism |
| 关键词[WOS] | STIMULATED INSULIN-SECRETION ; TRANSCRIPTION FACTOR FOXO1 ; RECEPTOR KINASE ; ADAPTER PROTEIN ; GENE-EXPRESSION ; OBESITY ; SH2-B ; ASSOCIATION ; ACTIVATION ; LEPTIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000331110000026 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/277]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Chen, Zheng,Morris, David L.,Jiang, Lin,et al. SH2B1 in beta-Cells Regulates Glucose Metabolism by Promoting beta-Cell Survival and Islet Expansion[J]. DIABETES,2014,63(2):585-595. |
| APA | Chen, Zheng,Morris, David L.,Jiang, Lin,Liu, Yong,&Rui, Liangyou.(2014).SH2B1 in beta-Cells Regulates Glucose Metabolism by Promoting beta-Cell Survival and Islet Expansion.DIABETES,63(2),585-595. |
| MLA | Chen, Zheng,et al."SH2B1 in beta-Cells Regulates Glucose Metabolism by Promoting beta-Cell Survival and Islet Expansion".DIABETES 63.2(2014):585-595. |
入库方式： OAI收割
来源：上海营养与健康研究所
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