胰岛素-葡萄糖-胰高血糖素动力学的简单机制模型及其对糖尿病管理的影响

摘要(中文译文)

胰岛素和葡萄糖的动态平衡受胰岛（Langerhans岛）的严密调控，胰岛中包含产生胰岛素的β细胞和产生胰高血糖素的α细胞。胰岛素通过使细胞能够利用葡萄糖获取能量来降低血糖，而胰高血糖素则通过刺激肝脏从非碳水化合物来源生成葡萄糖以及分解储存的糖原来升高血糖水平。维持安全的血糖水平至关重要，因为血糖过高（高血糖症）和过低（低血糖症）均可导致危及生命的后果。本研究建立了一个简单的三状态机制性胰岛素-葡萄糖-胰高血糖素模型，并利用接受静脉葡萄糖耐量试验（IVGTT）的猪的数据进行了验证。随后，该模型被用于研究接受外源性胰岛素治疗的患者中葡萄糖和胰高血糖素的动态变化，从而揭示不当糖尿病管理的影响。结果表明，延迟给予外源性胰岛素会通过抑制胰高血糖素的生成而增加低血糖风险。此外，对60分钟或更长的胰岛素半衰期进行了测试，结果显示如此延长的外源性胰岛素活性可抑制胰高血糖素对危急低血糖水平的反应。这一发现提示，较短的胰岛素半衰期可能有助于降低低血糖事件的风险。

Abstract

Insulin and glucose dynamics are tightly regulated by the pancreatic islets of Langerhans, which contain beta cells that produce insulin and alpha cells that produce glucagon. Insulin lowers blood glucose by enabling cells to access glucose for energy, while glucagon raises blood glucose levels by stimulating the liver to produce glucose from non-carbohydrate sources as well as breaking down stored glycogen. Maintaining safe blood glucose levels is crucial, as both high (hyperglycemia) and low (hypoglycemia) levels can lead to life threatening consequences. In this work, a simple three-state mechanistic insulin-glucose-glucagon model is developed and validated using data from pigs subjected to an intravenous glucose tolerance test (IVGTT). The model is then used to investigate glucose and glucagon dynamics in patients administering exogenous insulin, shedding light on the impact of improper diabetes management. The results show that delayed administration of exogenous insulin increases the risk of hypoglycemia by suppressing glucagon production. Furthermore, insulin half-lives of 60 minutes or longer were tested, revealing that such prolonged exogenous insulin activity can suppress glucagon's response to critically low glucose levels. This finding suggests that shorter insulin half-lives may help reduce the risk of hypoglycemic events.

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