A novel cyclopeptide from the cyclization of PACAP(1-5) with potent activity towards PAC1 attenuates STZ-induced diabetes

作者：Yu, Rongjie^*; Wang, Jingjing; Li, Juan; Wang, Ye; Zhang, Huahua; Chen, Jiansu; Huang, Lin; Liu, Xiaofei

来源：Peptides, 2010, 31(6): 1062-1067.

DOI：10.1016/j.peptides.2010.03.008

• PACAP
• Cyclization
• PAC1
• Agonist
• STZ-induced diabetes

The N-terminal deletion of pituitary adenylate cyclase-activating polypeptide (PACAP)(1-5) generates its own antagonist. The cyclopeptide C*HSDGIC*, which results from the cyclization of PACAP(1-5) with disulfide, was designed and synthesized. CHO cells expressing a PAC1 N/R splice variant (PAC1-CHO) were used to detect the potent activation of PAC1 by C*HSDGIC*. In vitro cell assays showed that C*HSDGIC* stimulated cAMP production and increased the viability of PAC1-CHO cells at micromolar concentrations, about 1000 fold that of PACAP. PACAP(6-38) blocked the effects of PACAP on the proliferation of PAC1-CHO cells but did not interfere with the effects of C*HSDGIC*, suggesting that the activation of PAC1 by C*HSDGIC* was independent of the binding of PAC1 to the C-terminus of PACAP. In experiments in vivo, 10 mu mol/kg C*HSDGIC* decreased the plasma glucose level, increased the plasma insulin level and improved glucose tolerance significantly (P < 0.01) when co-injected with STZ for 5 days. The results of these in vitro and in vivo studies of the biological characteristics of C*HSDGIC* reveal that it is a potent activator of PAC1.

• 出版日期2010-6
• 单位广东医科大学; 暨南大学