Experimental Models of Impaired Hypoglycaemia-Associated Counter-Regulation.
Experimental Models of Impaired Hypoglycaemia-Associated Counter-Regulation.
复制标题
低血糖相关反调节受损的实验模型。
DOI：
10.1016/j.tem.2020.05.008
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sankar A
中科院分区：
文献类型：
--
作者：
Sankar A
大约四分之一接受胰岛素治疗的糖尿病患者对低血糖（IAH）的认知受损。这种情况的特点是对低血糖的症状和行为反应逐渐减少，血糖进一步下降、意识不清和昏倒的风险增加。因此，IAH患者更频繁地经历严重的低血糖发作，导致显著的发病率和死亡率。IAH被认为是全身对反复胰岛素诱导的低血糖（RH）适应的结果，低血糖反调节反应（CRR）普遍存在缺陷。尽管有这一重要的见解，RH导致CRR减弱的确切病理生理机制尚不清楚。对IAH潜在机制的研究在人类和实验物种中采用了多种方案。动物模型的使用有许多研究的好处，包括转基因菌株的可用性前所未有的增加。然而，模拟受损的低血糖相关的反调节仍然具有挑战性，跨物种和方案的研究结果的适当解释更是如此。在这里，我们回顾了IAH的实验模型和受损的低血糖相关的反调节，重点是了解葡萄糖稳态的物种特异性变化。这一审查将有助于研究人员解释各种IAH研究的结果，并有助于该领域的进展。
Impaired awareness of hypoglycaemia (IAH) affects around a quarter of patients with diabetes who receive insulin treatment. This condition is characterised by a progressive reduction in symptomatic and behavioural responses to hypoglycaemia, increasing risk of deeper drops in blood glucose, unconsciousness, and collapse. Thus, patients with IAH experience severe hypoglycaemic episodes more frequently, resulting in significant morbidity and mortality. IAH is thought to develop as a consequence of whole-body adaptations to repeated insulin-induced hypoglycaemia (RH), with widespread deficits in the hypoglycaemia counter-regulatory response (CRR). Despite this important insight, the precise pathophysiology by which RH leads to an attenuated CRR is unknown. Studies into the underlying mechanisms of IAH have employed a variety of protocols in humans and experimental species. The use of animal models has many investigational benefits, including the unprecedented increase in the availability of transgenic strains. However, modelling impaired hypoglycaemia-associated counter-regulation remains challenging and appropriate interpretation of findings across species and protocols even more so. Here, we review the experimental modelling of IAH and impaired hypoglycaemia-associated counter-regulation, with a focus on understanding species-specific variation in glucose homeostasis. This review will aid investigators in interpreting outputs from different studies in IAH and aid progress in the field.