Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Division of Systems Medicine, School of Medicine, University of Dundee, Dundee, UK.
Trends Endocrinol Metab. 2020 Sep;31(9):691-703. doi: 10.1016/j.tem.2020.05.008. Epub 2020 Jun 17.
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.
低血糖意识受损（IAH）影响约四分之一接受胰岛素治疗的糖尿病患者。这种情况的特征是对低血糖的症状和行为反应逐渐减少，增加血糖深度下降、无意识和崩溃的风险。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 被认为是由于全身对反复胰岛素诱导的低血糖（RH）的适应而发展的，低血糖代偿反应（CRR）广泛受损。尽管有了这一重要的认识，但 RH 导致 CRR 减弱的确切病理生理学机制尚不清楚。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。动物模型的使用具有许多研究优势，包括空前增加了转基因品系的可用性。然而，模拟与低血糖相关的代偿失调仍然具有挑战性，更不用说在物种和方案之间进行适当的解释了。在这里，我们回顾了 IAH 和与低血糖相关的代偿失调的实验建模，重点是了解葡萄糖稳态的物种特异性变异。这篇综述将有助于研究人员解释 IAH 不同研究中的结果，并有助于该领域的进展。
