EMBO Mol Med：海蜗牛中Conkunitzin-S1可能治疗糖尿病的新药物

芋螺是海的天敌。他们通过注入猎物包含了不同物质的鸡尾酒来捕获鱼。蜗牛的毒液，所谓conopeptides是单一的组分，具有非凡的药理特性和开发潜力。

一个代表例子就是作为止痛药处方的芋螺毒素Ziconotid（Prialt）。芋螺毒素是第一个含有海洋生物物质的药物之一。在与来自加拿大和美国，在吕贝克大学研究团队和哥廷根大学的科学家合作研究的锥形蜗牛芋叶蝉的毒液。他们能够表现出一定的肽（Conkunitzin-S1），能改变胰岛素的胰腺细胞释放。他们的研究结果发表在EMBO Molecular Medicine杂志上。
 
葡萄糖是我们营养的一部分。当它进入消化系统，胰腺细胞释放胰岛素。糖化学分解到血液中。在2型糖尿病患者，这种机制被打乱，他们从患血糖水平过高或高血糖。新发现的物质，芋螺毒素S1期Conkunitzin，绑定到一个特定的钾离子通道在胰腺细胞，并导致暂时的胰岛素释放增加，但只有当血糖水平提高的时候。

大鼠口服葡萄糖耐受性测试之后，科学家们发现，Conkunitzin-S1不会导致低血糖。换句话说，一些传统的2型糖尿病药物的典型副作用不会发生。 Terlau说：我们研究工作在于发现管理肽口服的方式。

doi:10.1002/emmm.201200218
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Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion

Rocio K. Finol-Urdaneta, Maria S. Remedi, Walter Raasch, Stefan Becker, Robert B. Clark, Nina Strüver, Evgeny Pavlov, Colin G. Nichols, Robert J. French,*, Heinrich Terlau*

Glucose-stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage-gated potassium channels (K_v) generates an outward, ‘delayed rectifier’ potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several K_v channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone-snail peptide toxin, Conkunitzin-S1 (Conk-S1), which selectively blocks K_v1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk-S1 increases GSIS in isolated rat islets, likely by reducing K_v1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that K_v1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell K_v current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.