Imperial College London, 6th Floor, Commonwealth Building, Hammersmith Hospital, London, W12 0NN, United Kingdom.
Peptides. 2018 Feb;100:36-41. doi: 10.1016/j.peptides.2017.11.013.
Globally, 13% of the world's adult population is obese, and more than 400 million people suffer from diabetes. These conditions are both associated with significant morbidity, mortality and financial cost. Therefore, finding new pharmacological treatments is an imperative. Relative hyperglucagonaemia is seen in all types of diabetes, and has been implicated in its pathogenesis. Consequently, clinical trials are underway using drugs which block glucagon activity to treat type 2 diabetes. Conversely, exogenous glucagon can increase energy expenditure. Therefore, researchers are designing peptides that combine activation of the glucagon receptor with further incretin properties, which will treat obesity while mitigating the hyperglycaemic effects of glucagon. This review will discuss these conflicting physiological properties of glucagon, and the attempts to harness these effects pharmacologically.
全球范围内,有 13%的世界成年人口肥胖,超过 4 亿人患有糖尿病。这些情况都与严重的发病率、死亡率和经济成本有关。因此,寻找新的药物治疗方法是当务之急。所有类型的糖尿病患者都会出现相对高胰高血糖素血症,并且该病症与糖尿病的发病机制有关。因此,目前正在使用抑制胰高血糖素活性的药物进行治疗 2 型糖尿病的临床试验。相反,外源性胰高血糖素可以增加能量消耗。因此,研究人员正在设计将胰高血糖素受体激活与进一步的肠促胰岛素特性相结合的肽,这些肽将在治疗肥胖的同时减轻胰高血糖素的高血糖作用。本文将讨论胰高血糖素的这些相互矛盾的生理特性,以及尝试在药理学上利用这些特性的方法。