A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice
A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice
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DOI：
10.1039/c5fo00401b
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发表时间：
2015-01-01
期刊：
影响因子：
6.1
通讯作者：
Ohinata, Kousaku
中科院分区：
文献类型：
--
作者：
Ayabe, Tatsuhiro;Mizushige, Takafumi;Ohinata, Kousaku
我们发现，阿拉斯加鳕鱼蛋白的胰蛋白酶消化物在 KK-Ay 小鼠（一种 II 型糖尿病模型）中表现出降血糖作用。然后我们在消化物中寻找降糖肽。 Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) 是根据 ddY 小鼠胰岛素抵抗试验中的降糖活性选择的 HPLC 级分的峰来鉴定的。腹腔给药后ANGEVAQWR (3 mg kg(-1))降低了血糖水平。在其片段肽中，C端三肽Gln-Trp-Arg（QWR，1 mg kg(-1)）可降低血糖水平，表明C端对于降糖活性至关重要。 QWR 还增强了小鼠骨骼肌细胞系 C2C12 的葡萄糖摄取。 QWR 不会诱导丝氨酸/苏氨酸蛋白激酶 B (Akt) 和单磷酸腺苷激活蛋白激酶 (AMPK) 的磷酸化。我们还证明 QWR 可以降低 II 型糖尿病模型 NSY 和 KK-Ay 的血糖水平。
We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.