CHL1 promotes insulin secretion and negatively regulates the proliferation of pancreatic β cells.

Hemin Jiang, Yuwei Liu, Yu Qian, Ziyang Shen, Yunqiang He, Rui Gao, Min Shen, Shu Chen, Qi Fu, Tao Yang

Biochemical and biophysical research communications 2020 May 14

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Cell adhesion molecule L1-like protein (CHL1) is a member of neural recognition molecules of immunoglobulin superfamily primarily expressing in the nervous system. CHL1 regulates neuronal migration, axonal growth, and dendritic projection. Downregulation of CHL1 has been reported in β cells of patients with type 2 diabetes (T2DM). However, the detailed role of CHL1 in β cells has not been characterized. In this study, Real-Time PCR and Western blot were applied to investigate the tissue/cell distribution and expression of CHL1. Gain- or loss-of function studies were conducted in MIN6 cells to determine the effects of CHL1 on cell proliferation, apoptosis, cell cycle, and insulin secretion. Following silencing of CHL1 in MIN6 cells (si-CHL1), insulin secretion and the number of insulin secretary granules <50 nm from the cell membrane decreased in response to 20 mM glucose. Besides, silencing of CHL1 induced cell proliferation, reduced apoptosis, and prolonged S phase and shortened G1 phase of the cell cycle, contrary to overexpressing of CHL1. The inhibitor of ERK1/2MAPK eliminated the effect of CHL1 deficiency on the proliferation of MIN6 cells. In addition, high-fat diet could result in increased islet volume and β cell proliferation, decreased CHL1 expression and activation of ERK pathway in mice islets. Consequently, CHL1 expression was decreased in islets of high-fat induced mice, which resulted in cell proliferation via ERK pathway and regulation of the cell cycle through p53 pathway. These mechanisms may contribute to pancreatic β cell compensatory hyperplasia in obesity-induced pre-diabetes. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Hemin Jiang, Yuwei Liu, Yu Qian, Ziyang Shen, Yunqiang He, Rui Gao, Min Shen, Shu Chen, Qi Fu, Tao Yang. CHL1 promotes insulin secretion and negatively regulates the proliferation of pancreatic β cells. Biochemical and biophysical research communications. 2020 May 14;525(4):1095-1102