Neural control of the endocrine pancreas

The autonomic nervous system affects glucose metabolism partly through its connection to the pancreatic islet. Since its discovery by Paul Langerhans, the precise innervation patterns of the islet has remained elusive, mainly because of technical limitations. Using 3-dimensional reconstructions of axonal terminal fields, recent studies have determined the innervation patterns of mouse and human islets. In contrast to the mouse islet, endocrine cells within the human islet are sparsely contacted by autonomic axons. Instead, the invading sympathetic axons preferentially innervate smooth muscle cells of blood vessels. This innervation pattern suggests that, rather than acting directly on endocrine cells, sympathetic nerves may control hormone secretion by modulating blood flow in human islets. In addition to autonomic efferent axons, islets also receive sensory innervation. These axons transmit sensory information to the brain but also have the ability to locally release neuroactive substances that have been suggested to promote diabetes pathogenesis. We discuss recent findings on islet innervation, the connections of the islet with the brain, and the role islet innervation plays during the progression of diabetes.