α-cell electrophysiology and the regulation of glucagon secretion

in Journal of Endocrinology
Authors:
Rui GaoR Gao, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom of Great Britain and Northern Ireland

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Samuel AcremanS Acreman, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom of Great Britain and Northern Ireland

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Jinfang MaJ Ma, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom of Great Britain and Northern Ireland

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Fernando AbdulkaderF Abdulkader, Physiology and Biophysics, ICB-USP, Sao Paulo, Brazil

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Anna WendtA Wendt, Department of Clinical Sciences Malmö, Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö, Sweden

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Quan ZhangQ Zhang, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom of Great Britain and Northern Ireland

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Correspondence: Quan Zhang, Email: quan.zhang@ocdem.ox.ac.uk
Open access

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.

 

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