Specific deletion of CDC42 in pancreatic β cells attenuates glucose-induced insulin expression and secretion in mice

Xiang Qin He, Ning Wang, Juan Juan Zhao, Dan Wang, Cai Ji Wang, Lin Xie, Huai Yu Zheng, Shui Zhen Shi, Jing He, Jiliang Zhou, Hong Bo Xin, Ke Yu Deng

Research output: Contribution to journalArticle

Abstract

Insulin is a key hormone for maintaining glucose homeostasis in organisms. In general, deficiency of insulin synthesis and secretion results in type I diabetes, whereas insulin resistance leads to type 2 diabetes. Cell division cycle 42 (CDC42), a member of Rho GTPases family, has been shown as an essential regulator in the second phase of glucose-induced insulin secretion in pancreatic islets β cells in vitro. However, the effect of CDC42 on insulin expression has not been explored. Here we reported that the glucose-induced insulin expression and secretion were significantly inhibited in mice lacking CDC42 gene in pancreatic β cells (Rip-CDC42cKO) in vivo and in vitro. Deletion of CDC42 gene in pancreatic β cells did not affect survival or reproduction in mice. However, the Rip-CDC42cKO mice showed the systemic glucose intolerance and the decrease of glucose-induced insulin secretion without apparent alterations of peripheral tissues insulin sensitivity and the morphology of islets. Furthermore, we demonstrated that deletion of CDC42 gene in pancreatic β cells significantly attenuated the insulin expression through inhibiting the ERK1/2-NeuroD1 signaling pathway. Taken together, our study presents novel evidence that CDC42 is an important modulator in glucose-induced insulin expression as well as insulin secretion in pancreatic β cells.

Original languageEnglish (US)
Article number111004
JournalMolecular and Cellular Endocrinology
Volume518
DOIs
StatePublished - Dec 1 2020

Keywords

  • Cell division cycle 42 (CDC42)
  • Glucose homeostasis
  • Insulin expression
  • Insulin secretion
  • NeuroD1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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  • Cite this

    He, X. Q., Wang, N., Zhao, J. J., Wang, D., Wang, C. J., Xie, L., Zheng, H. Y., Shi, S. Z., He, J., Zhou, J., Xin, H. B., & Deng, K. Y. (2020). Specific deletion of CDC42 in pancreatic β cells attenuates glucose-induced insulin expression and secretion in mice. Molecular and Cellular Endocrinology, 518, [111004]. https://doi.org/10.1016/j.mce.2020.111004