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.Graphical abstract
Highlights
The islets of Langerhans, first described by Paul Langerhans in 1869, are dispersed throughout the exocrine tissue of the pancreas
Mathematical modelling suggests that a system in which the products of one partner, like the glucagon produced by the pancreatic alpha cell, have a stimulatory effect on its counterpart, while the other partner’s products, like the insulin secreted by the beta cell, have inhibitory effects, enables active regulation to maintain stable levels, something that is mandatory for the control of blood glucose concentration [1–3]
In the pancreatic alpha cell, proglucagon is processed by prohormone convertase 2 (PC2), resulting in the generation of glucagon and the so-called major proglucagon fragment, while in L cells, proglucagon is processed by PC1/3 resulting in the generation of GLP-1, among other products [16] (Fig. 2)
Summary
The islets of Langerhans, first described by Paul Langerhans in 1869, are dispersed throughout the exocrine tissue of the pancreas. Beta cells are the producers of the only blood glucose-lowering hormone in the body: insulin. By contrast, produce glucagon, a hormone that has blood glucose-increasing effects. Mathematical modelling suggests that a system in which the products of one partner, like the glucagon produced by the pancreatic alpha cell, have a stimulatory effect on its counterpart, while the other partner’s products, like the insulin secreted by the beta cell, have inhibitory effects, enables active regulation to maintain stable levels, something that is mandatory for the control of blood glucose concentration [1–3]. Beta cell-released factors, including, among others, insulin, Zn2+, ATP and γ-aminobutyric acid (GABA), have an inhibitory effect on glucagon secretion by alpha cells [5]. Glucose-stimulated insulin secretion (GSIS) involves multiple pathways: the triggering pathway, the metabolic amplifying pathway and neuronal or hormonal modifying pathways (Fig. 1). Activation of muscarinic acetylcholine receptors and subsequent initiation of the phospholipase C (PLC)/diacylglycerol (DAG)/protein kinase C (PKC) cascade improves GSIS
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