1526-P: Cephalic Phase Insulin Release Requires Alpha Cells

The glucose-independent rise of insulin levels immediately at the start of a meal is known as the cephalic phase of insulin release and is a neurally mediated physiological reflex. We recently found that IL-1β mediates cephalic phase insulin secretion by modulating parasympathetic neuronal transmission. It has been established that pancreatic islets are richly innervated by the parasympathetic nervous system, yet the mechanism underlying neuronally mediated insulin release at basal glucose, as seen in cephalic phase, remain to be studied. Methods: We assessed the role of glucagon in cephalic phase insulin secretion using a transgenic mouse model in which alpha cells are selectively ablated. Further, we isolated pancreatic islets of wild-type mice, as well as alpha cell-ablated mice, and assessed insulin and glucagon secretion at low glucose after stimulation with IL-1β, a muscarinic agonist (carbachol) and both combined. Results: We observed that mice lacking glucagon-producing alpha cells fail to exhibit a cephalic phase insulin response. In vitro, we found that muscarinic activation stimulated glucagon secretion at basal glucose, but not insulin secretion. Co-stimulating islets with the muscarinic agonist and IL-1β stimulated insulin secretion at basal glucose, and strikingly this was not the case in alpha cell-ablated islets. Conclusion: Cephalic phase of insulin release mediated by IL-1β stimulation of parasympathetic nerves requires pancreatic alpha cells. This beta-cell response may be mediated by glucagon. Disclosure K.A.Trimigliozzi: None. S.J.Wiedemann: None. D.T.Meier: None. L.Rachid: None. H.Mereau: None. M.Böni-schnetzler: None. M.Y.Donath: Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.