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

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.

• Authors: 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
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 518 Pg. 111004 (12 01 2020) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 32871224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cdc42 protein, mouse
• Insulin
• cdc42 GTP-Binding Protein
• Glucose

Topics

• Animals
• Cells, Cultured
• Gene Deletion
• Gene Expression (drug effects)
• Gene Knockdown Techniques
• Glucose (pharmacology)
• Insulin (genetics, metabolism)
• Insulin Resistance (genetics)
• Insulin Secretion (drug effects, genetics)
• Insulin-Secreting Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Organ Specificity (genetics)
• Rats
• Signal Transduction (drug effects, genetics)
• cdc42 GTP-Binding Protein (genetics)