PNAS:“智能”胰岛素预防糖尿病治疗过程中的低血糖症

2019-05-27 佚名 生物通

加州大学洛杉矶分校(UCLA)生物工程师和他们的同事开发了一种新型胰岛素,可以帮助那些使用这种药物治疗糖尿病的人预防低血糖。

加州大学洛杉矶分校(UCLA)生物工程师和他们的同事开发了一种新型胰岛素,可以帮助那些使用这种药物治疗糖尿病的人预防低血糖



目前正在对这种治疗方法进行潜在的临床试验评估,如果成功,可能会改变糖尿病的治疗方法。这项研究发表在《PNAS》上。

胰岛素是一种在胰腺中自然产生的激素。它帮助身体调节葡萄糖,葡萄糖通过食物被消耗并为身体提供能量。

当一个人的身体不能自然地产生胰岛素(1型糖尿病),或者不能有效地使用产生的胰岛素(2型糖尿病)时,就会发生糖尿病(影响全世界4亿多人)。在这两种情况下,医生会开出常规剂量的胰岛素来控制疾病。

一般来说,使用胰岛素的人需要用血糖仪或连续血糖监测系统监测血糖水平,然后相应地计算胰岛素剂量。同时,定期摄入碳水化合物对保持血糖水平正常很重要。这两个需求都必然会受到人为错误的影响,这可能会造成潜在的破坏性后果。

当血糖过低时,过量的胰岛素会造成低血糖。这可能导致癫痫发作、昏迷,甚至在极端情况下导致死亡。

作为一项安全检查,加州大学洛杉矶分校领导的研究小组开发了一种叫做i-胰岛素(i-insulin)的“智能”胰岛素,它可以防止血糖水平过低。

在体内,胰岛素起着“钥匙”的作用,帮助葡萄糖从血液中进入细胞。当胰岛素附着在细胞表面时,它会激活细胞内一种叫做葡萄糖转运蛋白的蛋白质,然后葡萄糖转运蛋白来到细胞表面,然后这个分子把血液中的葡萄糖带到细胞中。

研究小组在胰岛素中添加了一种额外的分子来制造新型智能胰岛素。这种被添加的分子,被称为葡萄糖转运抑制剂,在化学上阻止了到达表面的葡萄糖转运分子。它的存在并不能阻止所有葡萄糖进入,也不能永久性地阻止转运分子。相反,它属于动态过程的一部分,取决于有多少抑制剂和葡萄糖分子存在。

“我们的新胰岛素就像一把‘智能’钥匙,”该研究的主要负责人、加州大学洛杉矶分校工程学院生物工程教授Zhen Gu说。“胰岛素可以让葡萄糖进入细胞,但是添加的抑制剂分子可以防止血糖正常时过多的进入细胞。这使血糖保持在正常水平,并降低了低血糖的风险。”

“这种智能胰岛素也能对高血糖水平做出快速反应,”该研究的合着者、Gu研究小组的博士后研究员Jinqiang Wang补充说。“例如,饭后,当血糖水平上升时,血液中的胰岛素水平也迅速上升,这有助于使血糖水平正常化。”

研究小组在1型糖尿病小鼠身上测试了智能胰岛素。第一次注射后,i-胰岛素将血糖控制在正常范围内长达10小时,三小时后第二次注射低血糖保护得到延长。

“下一步是在决定是否进行临床试验之前,进一步评估改良胰岛素系统在动物模型中的长期生物相容性,”合着者、北卡罗来纳大学教堂山分校医学院糖尿病护理中心主任John Buse博士说。“如果意识到这一点,这将是糖尿病护理领域最令人兴奋的进展之一。”

Gu说:“新胰岛素有潜力根据反应时间和下一剂用药前它在体内的维持时间进行优化。它还可以通过其他方法给药,例如自动监测血糖水平的皮肤贴片或药片。”

作者已经申请了这项技术的专利。

原始出处:Wang J, Yu J, Zhang Y, et al. Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia. Proc Natl Acad Sci U S A. 2019 May 16.

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    2020-02-22 drwjr
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    2019-10-15 baoya
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    2019-05-27 misszhang

    谢谢MedSci提供最新的资讯

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