期刊
DIABETIC MEDICINE
卷 39, 期 12, 页码 -出版社
WILEY
DOI: 10.1111/dme.14973
关键词
glucose sensing; glycaemic variability; hypoglycaemia; impaired hypoglycaemia awareness; oxidative stress; review; type 1 diabetes
资金
- Juvenile Diabetes Research Foundation International
- Diabetes UK
- Tenovus Scotland
- Medical Research Council
- Wellcome Trust
- EU Innovative Medicines Initiative
- Helmsley Trust
Recurrent hypoglycaemia can lead to adaptive changes and damage in cells, as well as exacerbate oxidative stress and inflammation caused by chronic hyperglycaemia.
Aims People with type 1 and type 2 diabetes still frequently experience hypoglycaemia, which can be severe, leading to loss of consciousness. This review will examine the cellular consequences of recurrent hypoglycaemia. Methods This review, based on the Dorothy Hodgkin Lecture given at the Diabetes UK 2022 annual symposium by the author, will discuss our current understanding of the mechanisms by which hypoglycaemia is detected and the consequences of recurrent exposure to hypoglycaemia. Results Glucose-responsive cells found in the periphery as well as multiple areas of the brain are organised in a classical sensori-motor integrative network encompassing peripheral, hindbrain and hypothalamic components. The mechanism used by glucose-responsive neurons to detect hypoglycaemia parallel those of the classical glucose sensor the pancreatic ss-cell, namely in their use of glucokinase, K-ATP channels and AMP-activated protein kinase. Recurrent exposure to hypoglycaemia results in a series of cellular adaptations that may be designed to increase the resilience of cells to future hypoglycaemia. This review also highlights how hypoglycaemia, as an oxidative stressor, may also exacerbate chronic hyperglycaemia-induced increases in oxidative stress and inflammation, leading to damage to vulnerable brain regions. Conclusions Impaired awareness of hypoglycaemia follows the adaptation of central glucose-responsive neurons to repeated hypoglycaemia and may represent a form of memory called habituation. In diabetes, recurrent hypoglycaemia may have tissue consequences as a result of a profound disruption in the cellular response to a hypoglycaemic challenge that increases vulnerability to oxidative damage.
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