Alpha cell regulation of beta cell function
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REVIEW
Alpha cell regulation of beta cell function Tilo Moede 1
&
Ingo B. Leibiger 1
&
Per-Olof Berggren 1
Received: 13 February 2020 / Accepted: 15 April 2020 / Published online: 31 August 2020 # The Author(s) 2020
Abstract The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions.
Keywords Acetylcholine . Alpha cell . Beta cell . GLP-1 . Glucagon . Human . Islets . Mouse . Paracrine interaction . Review Abbreviations cAMP Cyclic adenosine monophosphate EPAC Exchange protein directly activated by cAMP GABA γ-Aminobutyric acid GiD Inhibitory designer GPCR GLP-1 Glucagon-like peptide 1 GPCR G-protein-coupled receptor GSIS Glucose-stimulated insulin secretion KATP ATP-dependent K+ (channel) PC Prohormone convertase PKA Protein kinase A
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05196-3) contains a slideset of the figures for download, which is available to authorised users. * Tilo Moede [email protected] 1
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska Sjukhuset L1:03, 17176 Stockholm, Sweden
Introduction The islets of Langerhans, first described by Paul Langerhans in 1869, are dispersed throughout the exocrine tissue of the pancreas. Each islet is an endocrine micro-organ consisting of multiple endocrine cell types, the two most prominent and numerous of which are beta and alpha cells. Beta cells are the producers of the only blood glucose-lowering hormone in the body: insulin. Alpha cells, by contrast, produce glucagon, a hormone that has blood glucose-increasing effects. One interesting and maybe more philosophical question to consider is why these two counteracting hormones are produced in such close proximity to each other. Mathematical modelling suggests that a system in which the products of one partner, lik
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