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

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

doi:10.1016/j.jgg.2021.11.006

Volume 49 Issue 3

Mar. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(3): 208-216

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

doi: 10.1016/j.jgg.2021.11.006

a National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, And Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011 China;
b Department of Urological Organ Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China;
c Department of Liver Organ Transplantation, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China;
d Department of Pathophysiology, Naval Medical University, Shanghai 200433, China

Funds:

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

Received Date: 2021-05-31
Accepted Date: 2021-11-15
Rev Recd Date: 2021-11-07
Publish Date: 2021-11-30

Abstract

Abstract

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 mTORC1 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 mTORC1 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 mTORC1 signaling.
- Grb10,
- β-cell mass,
- mTORC1,
- Dedifferentiation

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References(47)

References

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