title: 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.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Gylfe
authors.forename: A
authors.initials: A
authors.lastname: Tengholm
mesh_terms: D000818:Animals; D001069:Appetite Regulation; D019898:Autocrine Communication; D015306:Biogenic Monoamines / Q000502:physiology*; D020013:Calcium Signaling; D025461:Feedback, Physiological; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000294:innervation* / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D015306:Biogenic Monoamines; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon
keywords: glucagon; insulin; neurotransmitters; oscillations; pulsatile secretion; somatostatin