GRB10 regulates β-cell mass by inhibiting β-cell proliferation and stimulating β-cell dedifferentiation

作     者：Zixin Cai Fen Liu Yan Yang Dandan Li Shanbiao Hu Lei Song Shaojie Yu Ting Li Bilian Liu Hairong Luo Weiping Zhang Zhiguang Zhou Jingjing Zhang Zixin Cai;Fen Liu;Yan Yang;Dandan Li;Shanbiao Hu;Lei Song;Shaojie Yu;Ting Li;Bilian Liu;Hairong Luo;Weiping Zhang;Zhiguang Zhou;Jingjing Zhang

作者机构：National Clinical Research Center for Metabolic DiseasesMetabolic Syndrome Research CenterKey Laboratory of Diabetes ImmunologyMinistry of EducationAnd Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011 China Department of Urological Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Liver Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of PathophysiologyNaval Medical UniversityShanghai 200433China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2022年第49卷第3期

页      面：208-216页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China (91749118, 82070807, 81770775, 81730022) Natural Science Foundation of Hunan Province, China (2021JJ30976) National Key Research and Development Program (2019YFA0801903, 2018YFC2000100) 

主　　题：Grb10 β-cell mass mTORC1 Dedifferentiation 

摘      要：Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling.