D'Alessio David A
Durham, NC.
Trans Am Clin Climatol Assoc. 2025;135:231-239.
Traditionally, the islet hormone glucagon has been considered as a counterbalance to insulin, preventing hypoglycemia by promoting glucose release from the liver. This model is compatible both with clinical studies demonstrating that one of the initial endocrine responses to insulin-induced hypoglycemia is a rise in glucagon and with work demonstrating that glucagon signaling activates glycogenolysis in hepatocytes. This model has been extended to implicate glucagon in diabetogenesis, positing that the increased secretion of glucagon acts as a primary driver of hyperglycemia. However, recent work suggests an alternative set of actions for glucagon, including stimulation of insulin secretion and enhancement of hepatic insulin action. These recent findings align with the results of clinical trials using novel drugs that activate the glucagon receptor as part of a multi-receptor mechanism of action. Taken together, it appears that glucagon has distinct actions in the fed and fasted states, and glucagon receptor agonism has potential as a therapeutic approach to the treatment of diabetes.
传统上，胰岛激素胰高血糖素被认为是胰岛素的一种平衡机制，通过促进肝脏释放葡萄糖来预防低血糖。该模型既与临床研究结果相符，即胰岛素诱导的低血糖的初始内分泌反应之一是胰高血糖素升高，也与研究结果相符，即胰高血糖素信号激活肝细胞中的糖原分解。该模型已扩展到将胰高血糖素与糖尿病发生联系起来，认为胰高血糖素分泌增加是高血糖的主要驱动因素。然而，最近的研究表明胰高血糖素还有另一组作用，包括刺激胰岛素分泌和增强肝脏胰岛素作用。这些最新发现与使用新型药物激活胰高血糖素受体作为多受体作用机制一部分的临床试验结果一致。综上所述，胰高血糖素在进食和禁食状态下似乎具有不同的作用，并且胰高血糖素受体激动剂有潜力成为治疗糖尿病的一种治疗方法。
