Editors' ChoiceDiabetes

The Nerve of Those β Cells

Science Translational Medicine  29 Jun 2011:
Vol. 3, Issue 89, pp. 89ec98
DOI: 10.1126/scitranslmed.3002798

Abstract

First described in 1869 by a then-young medical student, the eponymous islets of Langerhans in the pancreas, site of secretion of numerous hormones, defined the foundations of endocrinology. Langerhans’ original description of small islands of cells and their closely associated nerve fibers is often cited as a classic example of the neuroendocrine gland. Over the years, however, we have come to appreciate that the cytoarchitecture of human islets is distinct from that of other animals.

Fast forward to 2011, and Rodriguez-Diaz et al. now report a new mechanism for neuroendocrine regulation of insulin secretion. Acetylcholine, thought to be supplied to islets by parasympathetic nerves, is known to stimulate secretion of insulin through receptors in the surface of pancreatic β cells. Using high-resolution confocal microscopy, Rodriguez-Diaz et al. demonstrated that human islets unexpectedly lacked the typical cholinergic neuronal innervation of mouse islets. Instead, they found evidence of acetylcholine within cytoplasmic vesicles of glucagon-producing α cells. The authors were able to elicit secretion of acetylcholine in denervated human islets by specifically stimulating α cells. This acetylcholine induced insulin secretion from the cultured islets in a dose-dependent manner. Because cholinergic stimulation sensitizes insulin-secreting β cells to subsequent stimuli, the authors hypothesized that α cell–derived acetylcholine could act in a paracrine fashion to prime nearby β cells. Indeed, insulin secretion from cultured islets that were subjected to repeated intervals of glucose elevation was potentiated by the addition of a cholinesterase inhibitor (which increases acetylcholine levels) and reduced by a cholinergic antagonist.

Although preliminary, these results point to a potential target for intervention in the treatment of diabetes. In reexamining dogma, the authors have discovered a unique feature of human islet biology. Future investigations will be critical for translating these findings to diabetes care and islet transplantation.

R. Rodriguez-Diaz et al., Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat. Med. 19 Jun 2011 (10.1038/nm.2371). [Abstract]