Abstract：
OBJECTIVE: Lacto-ghrestatin is abovine milk-derived peptide with the sequence of LIVTQTMKG, named LGP9 here. This study aimed to investigate protective effects of LGP9 on diabetic β cells in vivo and in vitro.
RESULTS: Type-1-diabetic (T1D) mice were generated by alloxan (ALX; 50 mg/kg, i.v.) and received a four-week treatment schedule of LGP9 at 0.3 mg/kg and 1 mg/kg. Related biochemical parameters were analyzed, and the protein expression was evaluated by Western blotting. The results showed that LGP9 decreased body weight, water consumption and blood glucose, improved oxygen stress and upregulated IRS2/PI3K/Akt signaling in the pancreas of T1D mice. To further investigate the mechanism of LGP9 on the preventive effect of the pancreas, Rin-m5f cells were treated with 15 mM alloxan and followed with LGP9 at 30 μM and 90 μM. The results indicated that LGP9 rebalanced oxygen stress levels, increased cell proliferation, decreased cell apoptosis and activated IRS2/PI3K/Akt signaling.
CONCLUSIONS: LGP9 ameliorated alloxan-injured pancreatic β cells through IRS2/PI3K/Akt signaling. The finding provides important help for the research and development of LGP9 in therapeutics of diabetes.
RESULTS: Type-1-diabetic (T1D) mice were generated by alloxan (ALX; 50 mg/kg, i.v.) and received a four-week treatment schedule of LGP9 at 0.3 mg/kg and 1 mg/kg. Related biochemical parameters were analyzed, and the protein expression was evaluated by Western blotting. The results showed that LGP9 decreased body weight, water consumption and blood glucose, improved oxygen stress and upregulated IRS2/PI3K/Akt signaling in the pancreas of T1D mice. To further investigate the mechanism of LGP9 on the preventive effect of the pancreas, Rin-m5f cells were treated with 15 mM alloxan and followed with LGP9 at 30 μM and 90 μM. The results indicated that LGP9 rebalanced oxygen stress levels, increased cell proliferation, decreased cell apoptosis and activated IRS2/PI3K/Akt signaling.
CONCLUSIONS: LGP9 ameliorated alloxan-injured pancreatic β cells through IRS2/PI3K/Akt signaling. The finding provides important help for the research and development of LGP9 in therapeutics of diabetes.
摘要：
目的：乳ghstatin是一种具有LIVTQTMKG序列的乳源肽，这里命名为LGP9。本研究旨在探讨LGP9对糖尿病β细胞的体内外保护作用。
结果：四氧嘧啶（ALX；50mg/kg，i.v.），并接受了0.3mg/kg和1mg/kg的LGP9的四周治疗方案。相关生化指标进行分析,并通过蛋白质印迹法评估蛋白质表达。结果表明，LGP9降低了体重，水消耗和血糖，改善T1D小鼠胰腺中的氧应激和上调IRS2/PI3K/Akt信号传导。进一步探讨LGP9对胰腺的预防作用机制,用15mM四氧嘧啶处理Rin-m5f细胞,然后用30μM和90μM的LGP9处理。结果表明，LGP9重新平衡了氧应激水平，细胞增殖增加，降低细胞凋亡和激活IRS2/PI3K/Akt信号。
结论：LGP9通过IRS2/PI3K/Akt信号传导改善四氧嘧啶损伤的胰腺β细胞。该发现为LGP9在糖尿病治疗中的研究和开发提供了重要帮助。
结果：四氧嘧啶（ALX；50mg/kg，i.v.），并接受了0.3mg/kg和1mg/kg的LGP9的四周治疗方案。相关生化指标进行分析,并通过蛋白质印迹法评估蛋白质表达。结果表明，LGP9降低了体重，水消耗和血糖，改善T1D小鼠胰腺中的氧应激和上调IRS2/PI3K/Akt信号传导。进一步探讨LGP9对胰腺的预防作用机制,用15mM四氧嘧啶处理Rin-m5f细胞,然后用30μM和90μM的LGP9处理。结果表明，LGP9重新平衡了氧应激水平，细胞增殖增加，降低细胞凋亡和激活IRS2/PI3K/Akt信号。
结论：LGP9通过IRS2/PI3K/Akt信号传导改善四氧嘧啶损伤的胰腺β细胞。该发现为LGP9在糖尿病治疗中的研究和开发提供了重要帮助。
