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.

胰岛素是维持生物体内葡萄糖稳态的关键激素。通常，胰岛素合成和分泌不足会导致I型糖尿病，而胰岛素抵抗会导致2型糖尿病。Rho GTPases家族成员之一的细胞分裂周期42（CDC42）已被证明是体外胰岛β细胞葡萄糖诱导的胰岛素分泌第二阶段的必需调节剂。但是，尚未研究CDC42对胰岛素表达的影响。在这里，我们报道了在体内和体外，胰腺β细胞（Rip-CDC42cKO）中缺乏CDC42基因的小鼠体内葡萄糖诱导的胰岛素表达和分泌受到明显抑制。。胰腺β细胞中CDC42基因的删除不影响小鼠的存活或繁殖。但是，Rip-CDC42cKO小鼠表现出全身性葡萄糖耐受不良和葡萄糖诱导的胰岛素分泌减少，而外周组织的胰岛素敏感性和胰岛形态没有明显改变。此外，我们证明了胰腺β细胞CDC42基因的缺失通过抑制ERK1 / 2-NeuroD1信号通路显着减弱了胰岛素表达。综上所述，我们的研究提供了新的证据，表明CDC42是葡萄糖诱导的胰岛素表达以及胰腺β细胞中胰岛素分泌的重要调节剂。