Neurotransmitter control of islet hormone pulsatility.

Abstract

Pulsatile secretion is an inherent property of hormone-releasing pancreatic islet cells. This secretory pattern is physiologically important and compromised in diabetes. Neurotransmitters released from islet cells may shape the pulses in auto/paracrine feedback loops. Within islets, glucose-stimulated β-cells couple via gap junctions to generate synchronized insulin pulses. In contrast, α- and δ-cells lack gap junctions, and glucagon release from islets stimulated by lack of glucose is non-pulsatile. Increasing glucose concentrations gradually inhibit glucagon secretion by α-cell-intrinsic mechanism/s. Further glucose elevation will stimulate pulsatile insulin release and co-secretion of neurotransmitters. Excitatory ATP may synchronize β-cells with δ-cells to generate coinciding pulses of insulin and somatostatin. Inhibitory neurotransmitters from β- and δ-cells can then generate antiphase pulses of glucagon release. Neurotransmitters released from intrapancreatic ganglia are required to synchronize β-cells between islets to coordinate insulin pulsatility from the entire pancreas, whereas paracrine intra-islet effects still suffice to explain coordinated pulsatile release of glucagon and somatostatin. The present review discusses how neurotransmitters contribute to the pulsatility at different levels of integration.