Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Department of Physiology, Institute of Neuroscience and Physiology, Metabolic Research Unit, University of Gothenburg, Göteborg, Sweden.
J Endocrinol. 2023 Jun 26;258(2). doi: 10.1530/JOE-22-0295. Print 2023 Aug 1.
Glucagon is the principal glucose-elevating hormone that forms the first-line defence against hypoglycaemia. Along with insulin, glucagon also plays a key role in maintaining systemic glucose homeostasis. The cells that secrete glucagon, pancreatic α-cells, are electrically excitable cells and use electrical activity to couple its hormone secretion to changes in ambient glucose levels. Exactly how glucose regulates α-cells has been a topic of debate for decades but it is clear that electrical signals generated by the cells play an important role in glucagon secretory response. Decades of studies have already revealed the key players involved in the generation of these electrical signals and possible mechanisms controlling them to tune glucagon release. This has offered the opportunity to fully understand the enigmatic α-cell physiology. In this review, we describe the current knowledge on cellular electrophysiology and factors regulating excitability, glucose sensing, and glucagon secretion. We also discuss α-cell pathophysiology and the perspective of addressing glucagon secretory defects in diabetes for developing better diabetes treatment, which bears the hope of eliminating hypoglycaemia as a clinical problem in diabetes care.
胰高血糖素是主要的升糖激素，构成低血糖的第一道防线。胰高血糖素与胰岛素一起，在维持全身葡萄糖稳态方面发挥着关键作用。分泌胰高血糖素的细胞，即胰岛α细胞，是可兴奋的电活性细胞，其激素分泌与环境葡萄糖水平的变化通过电活动偶联。几十年来，葡萄糖如何调节α细胞一直是一个争论的话题，但很明显，细胞产生的电信号在胰高血糖素分泌反应中起着重要作用。几十年的研究已经揭示了参与这些电信号产生的关键因素，以及可能控制它们以调节胰高血糖素释放的机制。这为充分了解神秘的α细胞生理学提供了机会。在这篇综述中，我们描述了细胞电生理学的最新知识，以及调节兴奋性、葡萄糖感应和胰高血糖素分泌的因素。我们还讨论了α细胞的病理生理学，以及解决糖尿病中胰高血糖素分泌缺陷的观点，以开发更好的糖尿病治疗方法，从而有希望消除糖尿病治疗中低血糖这一临床问题。
