Liu Yunlong, Gao Zhangzhao, Guo Qingtuo, Wang Tao, Lu Conger, Chen Ying, Sheng Qing, Chen Jian, Nie Zuoming, Zhang Yaozhou, Wu Wutong, Lv Zhengbing, Shu Jianhong
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Mar Drugs. 2014 Mar 13;12(3):1512-29. doi: 10.3390/md12031512.
To determine whether cholera toxin B subunit and active peptide from shark liver (CTB-APSL) fusion protein plays a role in treatment of type 2 diabetic mice, the CTB-APSL gene was cloned and expressed in silkworm (Bombyx mori) baculovirus expression vector system (BEVS), then the fusion protein was orally administrated at a dose of 100 mg/kg for five weeks in diabetic mice. The results demonstrated that the oral administration of CTB-APSL fusion protein can effectively reduce the levels of both fasting blood glucose (FBG) and glycosylated hemoglobin (GHb), promote insulin secretion and improve insulin resistance, significantly improve lipid metabolism, reduce triglycerides (TG), total cholesterol (TC) and low density lipoprotein (LDL) levels and increase high density lipoprotein (HDL) levels, as well as effectively improve the inflammatory response of type 2 diabetic mice through the reduction of the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Histopathology shows that the fusion protein can significantly repair damaged pancreatic tissue in type 2 diabetic mice, significantly improve hepatic steatosis and hepatic cell cloudy swelling, reduce the content of lipid droplets in type 2 diabetic mice, effectively inhibit renal interstitial inflammatory cells invasion and improve renal tubular epithelial cell nucleus pyknosis, thus providing an experimental basis for the development of a new type of oral therapy for type 2 diabetes.
为了确定霍乱毒素B亚基与鲨鱼肝活性肽(CTB - APSL)融合蛋白在2型糖尿病小鼠治疗中是否发挥作用,将CTB - APSL基因克隆并在家蚕杆状病毒表达载体系统(BEVS)中表达,然后以100 mg/kg的剂量对糖尿病小鼠进行为期五周的口服给药。结果表明,口服CTB - APSL融合蛋白可有效降低空腹血糖(FBG)和糖化血红蛋白(GHb)水平,促进胰岛素分泌并改善胰岛素抵抗,显著改善脂质代谢,降低甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白(LDL)水平并提高高密度脂蛋白(HDL)水平,还可通过降低炎症细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平有效改善2型糖尿病小鼠的炎症反应。组织病理学显示,该融合蛋白可显著修复2型糖尿病小鼠受损的胰腺组织,显著改善肝脂肪变性和肝细胞浊肿,降低2型糖尿病小鼠的脂滴含量,有效抑制肾间质炎性细胞浸润并改善肾小管上皮细胞核固缩,从而为开发新型2型糖尿病口服治疗药物提供了实验依据。