Department of Agricultural Biology, National Academy of Agricultural Science, RDA, 61 Seodun-Dong, Kwunseon-gu, Suwon 441-100, Korea.
J Toxicol Environ Health A. 2010;73(21-22):1511-20. doi: 10.1080/15287394.2010.511575.
The molecular mechanisms underlying the glucose-lowering effects of Isaria sinclairii (Cicada Dongchunghacho), a fungus cultured on silkworm, are not fully elucidated. Thus the glucose-lowering effects of I. sinclairii as potential an antidiabetic agent were investigated in C57BL/6 obese (ob/ob) mice over a 6-mo period. For a period of 26 wk, ob mice were administered either 5 or 10% (w/w) I. sinclairii powder (IS), 10% dry mulberry leaf powder (ML), or 10% silkworm (SW) powder in the standard diet while a control group received only standard diet. The ML and SW preparations served as positive controls. Isaria sinclairii at 10% in the diet was more effective in reducing body weight compared to 10% ML, 10% SW, or 5% I. sinclairii. The fall in blood glucose levels in the groups treated for 26 wk was greater in both IS groups at 1 mo compared to ML or SW but equal in all groups at 6 mo. Microarray analyses were performed with a mouse 7.4K cDNA clone set array to identify the gene-expression profiles for the IS-, ML-, and SW-exposed ob mouse liver. The 10% IS group, compared to control, showed that 15 genes including glucokinase (Gk-rs1) and LDL receptor relating protein 1 were upregulated and 12 genes including cell translocation gene2 (antiproliferative) and hydroxyprostaglandin dehydrogenase (Hpgd 15) were downregulated. Upregulation of Gk-rs 1 and downregulation of Hpgd 15 were previously shown to occur in drug-induced suppression of diabetes. With ML, Lepr (leptin receptor), Pik3cb (phosphatidylinositol 3-kinase), and Prodh (proline dehydrogenase), related to suppression of diabetes, were upregulated. In the case of SW, the enzymes (G2an, alpha glucosidase 2) and Mmp9 (matrix metalloproteinase 9) involved in elevation of blood glucose levels were both downregulated. Data suggest that I. sinclarii is effective in lowering blood glucose due to the upregulation of glucokinase (Gk-rs1) and downregulation of hydroxyprostaglandin dehydrogenase (Hpgd 15), both associated with suppression of diabetes, indicating that microarray analysis is a useful tool to assess pharmacological potency of therapeutic compounds.
蝉拟青霉（Isaria sinclairii）是一种寄生于蚕的真菌，其降血糖的分子机制尚未完全阐明。因此，本研究旨在探究蝉拟青霉作为一种潜在抗糖尿病药物在 C57BL/6 肥胖（ob/ob）小鼠中的降血糖作用，为期 6 个月。在 26 周的时间里，ob 小鼠喂食 5%或 10%（w/w）的蝉拟青霉粉末（IS）、10%干桑叶粉末（ML）或 10%蚕粉（SW），而对照组只喂食标准饮食。ML 和 SW 制剂作为阳性对照。饮食中 10%的蝉拟青霉比 10%ML、10%SW 或 5%IS 更能有效降低体重。与 ML 或 SW 相比，在 26 周治疗后 1 个月时，两组 IS 组的血糖水平下降更大，但在 6 个月时所有组的血糖水平均相等。使用小鼠 7.4K cDNA 克隆组芯片进行微阵列分析，以鉴定 IS、ML 和 SW 暴露的 ob 鼠肝的基因表达谱。与对照组相比，10%IS 组有 15 个基因（包括葡萄糖激酶（Gk-rs1）和 LDL 受体相关蛋白 1）上调，12 个基因（包括细胞易位基因 2（抗增殖）和羟基前列腺素脱氢酶（Hpgd 15）下调。先前的研究表明，在药物诱导的糖尿病抑制中，Gk-rs1 的上调和 Hpgd 15 的下调都发生了。用 ML 处理时，与糖尿病抑制相关的 Lepr（瘦素受体）、Pik3cb（磷脂酰肌醇 3-激酶）和 Prodh（脯氨酸脱氢酶）上调。在 SW 的情况下，参与血糖升高的酶（G2an、α-葡萄糖苷酶 2）和 Mmp9（基质金属蛋白酶 9）都下调。数据表明，由于葡萄糖激酶（Gk-rs1）的上调和羟基前列腺素脱氢酶（Hpgd 15）的下调，蝉拟青霉在降低血糖方面是有效的，这两者都与糖尿病的抑制有关，表明微阵列分析是评估治疗化合物药理学效力的有用工具。
