Unravelling innervation of pancreatic islets

Abstract

The central and peripheral nervous systems play critical roles in regulating pancreatic islet function and glucose metabolism. Over the last century, in vitro and in vivo studies along with examination of human pancreas samples have revealed the structure of islet innervation, investigated the contribution of sympathetic, parasympathetic and sensory neural pathways to glucose control, and begun to determine how the structure and function of pancreatic nerves are disrupted in metabolic disease. Now, state-of-the art techniques such as 3D imaging of pancreatic innervation and targeted in vivo neuromodulation provide further insights into the anatomy and physiological roles of islet innervation. Here, we provide a summary of the published work on the anatomy of pancreatic islet innervation, its roles, and evidence for disordered islet innervation in metabolic disease. Finally, we discuss the possibilities offered by new technologies to increase our knowledge of islet innervation and its contributions to metabolic regulation.

Keywords: 3D imaging; Innervation; Islet; Nerve; Neuromodulation; Pancreas; Parasympathetic; Review; Sensory; Sympathetic.

Fig. 1

Summary of pancreatic innervation. (a) Pancreatic sympathetic preganglionic neurons arise from the intermediolateral column of the spinal cord and project to the coeliac ganglion. Postganglionic sympathetic neurons project from the coeliac ganglion to the pancreas. (b) Pancreatic parasympathetic efferent preganglionic neurons originate from the dorsal motor nucleus of the vagus and travel in the vagus nerve to intrapancreatic ganglia. Postganglionic parasympathetic neurons project from intrapancreatic ganglia to the islets and to other intrapancreatic ganglia to form a network within the pancreas. (c) Pancreatic parasympathetic afferent neurons with terminals in the pancreas and cell bodies in the nodose ganglia travel in the vagus nerve to provide sensory information from the pancreas to the nucleus of the solitary tract. (d) Pancreatic spinal sensory neurons with cell bodies in the dorsal root ganglia convey sensory information from the pancreas to the dorsal horn of the spinal cord and then to the CNS. (e) Enteropancreatic neurons with cell bodies in the myenteric ganglia of the stomach and duodenum project to the pancreas. This figure is available as part of a downloadable slideset

Fig. 2

Summary of mouse islet innervation. Pancreatic islets are innervated by the autonomic nervous system. Preganglionic parasympathetic efferent fibres (dark blue) innervate intrapancreatic ganglia. Postganglionic parasympathetic efferent fibres project from intrapancreatic ganglia to the islets (green). Sympathetic efferent fibres (red) innervate intrapancreatic ganglia, islets and blood vessels. Islets also receive input from enteric neurons (yellow). Sensory information is transmitted through parasympathetic afferents (light blue) and spinal afferents (purple). Arrows show the direction of transmission. This figure is available as part of a downloadable slideset