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首页> 外文期刊>Cell biology international. >DPP IV resistance and insulin releasing activity of a novel di-substituted analogue of glucose-dependent insulinotropic polypeptide, (Ser(2)-Asp(13))GIP.
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DPP IV resistance and insulin releasing activity of a novel di-substituted analogue of glucose-dependent insulinotropic polypeptide, (Ser(2)-Asp(13))GIP.

机译：DPP IV抵抗和胰岛素依赖性促胰岛素多肽（Ser（2）-Asp（13））GIP的新型二取代类似物的胰岛素释放活性。

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摘要

Structure-function studies suggest that preservation of the N-terminus and secondary structure of glucose-dependent insulinotropic polypeptide (GIP) is important for biological activity. Therefore, a novel di-substituted analogue of GIP, (Ser(2)-Asp(13))GIP, containing a negatively charged Asp residue in place of an Ala in position 13, was synthesised and evaluated for in vitro biological activity. Incubation with dipeptidyl peptidase IV (DPP IV) showed the half-lives of GIP and (Ser(2)-Asp(13))GIP to be 2.3 and >4h, respectively. Insulin releasing studies in clonal pancreatic BRIN-BD11 cells demonstrated that (Ser(2)-Asp(13))GIP (10(-12)to 10(-7)mol/l) was significantly less potent (60-90%; P<0.05 to P<0.001) than native GIP. The peptide failed to display antagonistic properties as it did not significantly alter insulin secretion when incubated in the presence of GIP (10(-7)mol/l). These results demonstrate that despite increased resistance to DPP IV, substituting Ala in position 13 with a negatively charged Asp, thus producing the di-substituted analogue (Ser(2)-Asp(13))GIP, significantly reduces biological activity, most likely due to modifications within the secondary structure.
机译：结构功能研究表明，葡萄糖依赖性促胰岛素多肽（GIP）的N端和二级结构的保存对于生物活性很重要。因此，合成了一种新型的GIP二取代类似物（Ser（2）-Asp（13））GIP，它在位置13处取代了Ala，带有带负电的Asp残基，并进行了体外生物活性评估。与二肽基肽酶IV（DPP IV）孵育显示GIP和（Ser（2）-Asp（13））GIP的半衰期分别为2.3和> 4h。克隆胰腺BRIN-BD11细胞中的胰岛素释放研究表明（Ser（2）-Asp（13））GIP（10（-12）至10（-7）mol / l）的效价明显较低（60-90％; P <0.05至P <0.001）。当在GIP（10（-7）mol / l）存在下温育时，该肽不会显着改变胰岛素分泌，因此无法显示拮抗特性。这些结果表明，尽管增加了对DPP IV的抗性，但在13位上用带负电荷的Asp取代了Ala，从而产生了二取代的类似物（Ser（2）-Asp（13））GIP，其生物活性显着降低，这很可能是由于在二级结构中进行修改。

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