Choi Jae-Suk, Kim Joo-Wan, Park Jeong Been, Pyo Sang Eun, Hong Yong-Ki, Ku Sae Kwang, Kim Mi-Ryung
Major in Food Biotechnology, Division of Bioindustry, College of Medical and Life Sciences, Silla University, Sasang-gu, Busan 46958, Republic of Korea.
Aribio Inc., Byeoksan Digital Valley, Yeongdeungpo-gu, Seoul 07286, Republic of Korea.
Int J Mol Med. 2017 Jun;39(6):1437-1451. doi: 10.3892/ijmm.2017.2967. Epub 2017 Apr 26.
Freshwater animal proteins have long been used as nutrient supplements. In this study, melanian snail (Semisulcospira libertina) protein hydrolysates (MPh) were found to exert anti-diabetic and protective effects against liver and kidney damage in mice with type II diabetes adapted to a 45% kcal high-fat diet (HFD). The hypoglycemic, hepatoprotective and nephroprotective effects of MPh were analyzed after 12 weeks of the continuous oral administration of MPh at 125, 250 and 500 mg/kg. Diabetic control mice exhibited an increase in body weight, and blood glucose and insulin levels, with a decrease in serum high-density lipoprotein (HDL) levels. In addition, an increase in the regions of steatohepatitis, hepatocyte hypertrophy, and lipid droplet deposit-related renal tubular vacuolation degenerative lesions were detected, with noticeable expansion and hyperplasia of the pancreatic islets, and an increase in glucagon- and insulin-producing cells, insulin/glucagon cell ratios in the endocrine pancreas and hepatic lipid peroxidation, as well as decreased zymogen contents. Furthermore, a deterioration of the endogenous antioxidant defense system was observed, with reduced glucose utilization related hepatic glucokinase (GK) activity and an increase in hepatic gluconeogenesis-related phosphoenolpyruvate carboxykinase (PEPCK) and glucose‑6-phosphatase (G6pase) activity. However, all of these diabetic complications were significantly inhibited by oral treatment with MPh in a dose-dependent manner. In addition, the marked dose-dependent inhibition of hepatic lipid peroxidation, the depletion of the liver endogenous antioxidant defense system, and changes in hepatic glucose-regulating enzyme activities were also observed. The results of this study suggest that MPh exerts potent anti-diabetic effects, along with the amelioration of related complications in mice with type II diabetes. The overall effects of MPh at a dose of 125 mg/kg on HFD-induced diabetes and related complications were similar or more potent than those of metformin (250 mg/kg).
淡水动物蛋白长期以来一直被用作营养补充剂。在本研究中，发现黑螺（Semisulcospira libertina）蛋白水解物（MPh）对适应45%千卡高脂饮食（HFD）的II型糖尿病小鼠具有抗糖尿病作用，并对肝脏和肾脏损伤具有保护作用。在以125、250和500 mg/kg的剂量连续口服MPh 12周后，分析了MPh的降血糖、肝脏保护和肾脏保护作用。糖尿病对照小鼠体重增加，血糖和胰岛素水平升高，血清高密度脂蛋白（HDL）水平降低。此外，检测到脂肪性肝炎区域增加、肝细胞肥大以及与脂质滴沉积相关的肾小管空泡变性病变，胰岛明显扩张和增生，内分泌胰腺中产生胰高血糖素和胰岛素的细胞增加、胰岛素/胰高血糖素细胞比率增加以及肝脏脂质过氧化增加，同时酶原含量降低。此外，观察到内源性抗氧化防御系统恶化，与葡萄糖利用相关的肝葡萄糖激酶（GK）活性降低，与肝糖异生相关的磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6pase）活性增加。然而，口服MPh以剂量依赖性方式显著抑制了所有这些糖尿病并发症。此外，还观察到肝脏脂质过氧化的显著剂量依赖性抑制、肝脏内源性抗氧化防御系统的消耗以及肝脏葡萄糖调节酶活性的变化。本研究结果表明，MPh对II型糖尿病小鼠具有显著的抗糖尿病作用，并能改善相关并发症。125 mg/kg剂量的MPh对HFD诱导的糖尿病和相关并发症的总体作用与二甲双胍（250 mg/kg）相似或更强。
