Anti-Diabetic Effects of CTB-APSL Fusion Protein in Type 2 Diabetic Mice

Yunlong Liu,Jian Chen,Qing Sheng,Tao Wang,Yaozhou Zhang,Wutong Wu,Jianhong Shu,Zhangzhao Gao,Ying Chen,Conger Lu,Zuoming Nie,Zhengbing Lv,Qingtuo Guo

doi:10.3390/md12031512

Abstract

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.

Highlights

Diabetes mellitus is a common chronic metabolic disease, usually caused by the interaction of genetic and environmental factors [1]
We evaluated the anti-diabetes effects of the cholera toxin B subunit and active peptide from shark liver (CTB-APSL) fusion protein in type 2 diabetic mice
We found that the CTB-APSL fusion protein has good activity against type 2 diabetes and effectively improves its complications

Summary

Introduction

Diabetes mellitus is a common chronic metabolic disease, usually caused by the interaction of genetic and environmental factors [1]. It is characterized by a lack of insulin secretion (relative and absolute) and insulin resistance [2], always leading to metabolism disorders of fat, protein and carbohydrate [3], and is likely to produce serious complications involving some of the vital organs, including the heart, blood vessels, nerves, eyes and kidneys as well as causing tissue lesions [4]. The research and development of low toxicity and long-acting diabetes drugs, has a very significant impact on the prevention and treatment of diabetes and on improving people’s quality of life. Diabetes is mainly divided into type 1 diabetes and type 2 diabetes, wherein more than

Results

Discussion

Conclusion