Neuronal Regulation of the Pancreatic Beta Cell Mass

The pancreas is innervated by sympathetic, parasympathetic, glial, and sensory neurons. I have uncovered a mechanism whereby the sympathetic neurons act to negatively regulate the beta cell mass of the pancreas by decreasing proliferation, and in some instances, increasing apoptosis. 

To address the neuron type that might act to negatively regulate the beta cell mass I utilized the mouse beta cell line, Min6. I treated this cell line with a battery of factors that are deposited by the pancreas innervating neurons. Of these, the products specific to the sympathetic neurons elicited an anti-proliferative and pro-apoptotic response. Further, the products acted in a receptor specific manner that led to the investigation of the Alpha-2-Adrenergic receptor. Having established this receptors role in the elicitation of apoptosis in a cell line, I moved forward to utilizing primary mouse Islets from mice. Treatment of the Islets with the Alpha-2-Adrenergic receptor agonists generated a decrease in the proliferative capacity of the structures. Alteration of the Islets from the native ball like cluster morphology, to a flat culture revealed the initiation of apoptosis upon similar agonist treatment. Utilization of Islets lacking the Alpha-2-Adrenergic receptor revealed that this effect was indeed receptor specific. Currently, In vivo experiments have been initiated to determine whether these findings can be paralleled In Vivo. Additionally, we are attempting to dissect the observation whereby the tissue morphology can dictate the response (quiescence or apoptosis) upon treatment with factors that signal through the Alpha-2-Adrenergic receptor.