HBP1 inhibits the development of type 2 diabetes mellitus through transcriptional activation of the IGFBP1 gene.
HBP1 inhibits the development of type 2 diabetes mellitus through transcriptional activation of the IGFBP1 gene.
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HBP1 通过 IGFBP1 基因的转录激活抑制 2 型糖尿病的发展
DOI：
10.18632/aging.204364
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发表时间：
2022-11-02
期刊：
影响因子：
5.2
通讯作者：
Zhang, Xiaowei
中科院分区：
文献类型：
--
作者：
Cheng, Yuning;Yang, Ruixiang;Zhou, Yue;Wang, Jiyin;Zhang, Tongjia;Wang, Shujie;Li, Hui;Jiang, Wei;Zhang, Xiaowei
2型糖尿病（T2 DM）是一种慢性代谢性疾病，在全球范围内高度流行，其特征是葡萄糖和脂质代谢紊乱。然而，致病机制尚未完全确定。在这里，我们发现HMG盒转录因子1（HBP 1）参与T2 DM，它的缺陷在小鼠中阐明了糖尿病的特征。此外，我们通过RNA测序进行了筛选，发现HBP 1激活胰岛素样生长因子结合蛋白1（IGFBP 1）基因的转录。此外，胰岛素和棕榈酸减少HBP 1蛋白的表达，并抑制其结合IGFBP 1启动子。此外，HBP 1通过IGFBP 1降低血清游离胰岛素样生长因子1（IGF-1）浓度，并抑制PI 3 K/AKT信号通路。这形成了胰岛素/HBP 1/IGFBP 1负反馈调节环，以动态调节血糖和胰岛素浓度。这些发现阐明了HBP 1及其负反馈调节环影响T2 DM发生发展的机制，为T2 DM的治疗提供了新的理论依据和潜在的治疗靶点。
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is highly prevalent worldwide and characterized by glucose and lipid metabolism disorders. However, the pathogenic mechanisms have not been fully established. Here, we found that HMG-box transcription factor 1 (HBP1) is involved in T2DM and that its deficiency in mice aggravates the features of diabetes. In addition, we undertook screening by RNA sequencing and found that HBP1 activates the transcription of the insulin-like growth factor binding protein 1 (IGFBP1) gene. Moreover, Insulin and palmitic acid reduced HBP1 protein expression and inhibited its binding to the IGFBP1 promoter. Furthermore, HBP1 reduced the serum free insulin-like growth factor 1 (IGF-1) concentration through IGFBP1 and inhibited the PI3K/AKT signaling pathway. This forms an insulin/HBP1/IGFBP1 negative feedback regulatory loop to dynamically regulate blood glucose and insulin concentrations. These findings have elucidated a mechanism whereby HBP1 and its negative feedback regulatory loop influence the development of T2DM, thereby providing a new theoretical basis and potential therapeutic target for T2DM.
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影响因子：
4.8
作者：
Chahal, Jaspreet;Chen, Ching-Chu;Villafuerte, Betty C.
通讯作者：
Villafuerte, Betty C.
影响因子：
5.3
作者：
Berasi, SP;Xiu, M;Paulson, KE
通讯作者：
Paulson, KE
影响因子：
--
作者：
Reinehr, Thomas;Kleber, Michaela;Roth, Christian L.
通讯作者：
Roth, Christian L.
HBP1 介导的 AFP 转录抑制可抑制肝癌进展。
DOI：
10.1186/s13046-021-01881-2
发表时间：
2021-04-01
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Cao Z;Cheng Y;Wang J;Liu Y;Yang R;Jiang W;Li H;Zhang X
通讯作者：
Zhang X
影响因子：
81.5
作者：
DeFronzo, Ralph A.;Ferrannini, Ele;Weiss, Ram
通讯作者：
Weiss, Ram