Structural Refinement of Glucagon for Therapeutic Use
Structural Refinement of Glucagon for Therapeutic Use
复制标题
DOI：
10.1021/acs.jmedchem.9b01493
复制
发表时间：
2020-04-09
影响因子：
7.3
通讯作者：
DiMarchi, Richard D.
中科院分区：
文献类型：
--
作者：
Chabenne, Joseph R.;Mroz, Piotr A.;DiMarchi, Richard D.
胰高血糖素对抗胰岛素对葡萄糖代谢的影响，并在低血糖症的治疗中作为急救药物。急性低血糖是胰岛素依赖型糖尿病的常见症状，是纠正高血糖的主要障碍，是长期微血管并发症的主要原因。因此，对改善胰高血糖素治疗的兴趣重新抬头，包括非常规液体制剂、替代给药途径和具有优化生物物理性质的新型类似物。这些选择共同最小化胰高血糖素递送的复杂性，并使其能够以常规紧急救援试剂盒不可行的方式应用。这些进展间接促进了胰高血糖素激动剂与其他激素的综合使用，其方式与胰高血糖素拮抗作用的长期追求背道而驰。这篇综述总结了胰高血糖素优化的新方法，这些方法可能应用于更广泛的治疗肽家族，其中可能遇到生物物理挑战。
Glucagon counters insulin's effects on glucose metabolism and serves as a rescue medicine in the treatment of hypoglycemia. Acute hypoglycemia, a common occurrence in insulin-dependent diabetes, is the central obstacle to correcting high blood glucose, a primary cause of long-term microvascular complications. As a result, there has been a resurgence of interest in improved glucagon therapy, including nonconventional liquid formulations, alternative routes of administration, and novel analogs with optimized biophysical properties. These options collectively minimize the complexity of glucagon delivery and enable its application in ways not feasible with conventional emergency rescue kits. These advances have indirectly promoted the integrated use of glucagon agonism with other hormones in a manner that runs counter to the long-standing pursuit of glucagon antagonism. This review summarizes novel approaches to glucagon optimization, methods with potential application to the broader family of therapeutic peptides, where biophysical challenges may be encountered.