Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques

Meal-induced insulin secretion is thought to be regulated primarily by abso rbed nutrients and incretin hormones released from the gastrointestinal tra ct. In addition, the parasympathetic nervous system (PNS) is known to media te preabsorptive, or cephalic phase, insulin secretion. Despite evidence th at the PNS remains activated during the absorptive phase of the meal, its r ole in mediating postprandial insulin secretion has not been established. T o study the role of the PNS in absorptive phase insulin release, we measure d plasma concentrations of glucose as well as islet hormones and incretins in six healthy rhesus monkeys before and for 60 min after meals while they were infused with saline (control), atropine (muscarinic blockade), or trim ethaphan (nicotinic blockade). During the infusion of saline, plasma levels of glucose, pancreatic polypeptide (PP), insulin, glucose dependent insuli notropic polypeptide, and glucagon-like peptide-1 increased promptly after meal ingestion and remained elevated throughout the 60 min of the study. Th e PP response was nearly abolished in animals treated with trimethaphan, in dicating functional blockade of PNS input to the islet, and in contrast to the control study, there were minimal changes in plasma concentrations of g lucose, incretin hormones, and insulin. Because trimethaphan inhibited glyc emic and incretin stimuli in addition to blocking PNS input to the islet, i t was not possible to discern the relative roles of these factors in the st imulation of insulin secretion. Atropine also significantly decreased PNS t ransmission to the islet, as reflected by PP levels similar to those observ ed with trimethaphan. Unlike the trimethaphan study, plasma glucose levels rose normally during atropine treatment and were similar to those in the co ntrol study over the course of the experiments (114 +/- 22 and 132 +/- 23 m mol/L.60 min, respectively). In addition, the rise in plasma glucagon-like peptide-1 following the meal was not suppressed by atropine, and the glucos e dependent insulinotropic polypeptide responses were only modestly decreas ed. Despite the significant increases in circulating glucose and incretins, plasma insulin levels were greatly attenuated by atropine, so that the 60 min responses were more comparable to those during trimethaphan treatment t han to those in the control study (atropine, 3,576 +/- 1,284; trimethaphan, 4,128 +/- 2,616; control, 15,834 +/- 5,586 pmol/L.60 min; P < 0.05). Thus, muscarinic blockade markedly suppressed the meal-induced insulin response despite normal postprandial glycemia and significant elevations of incretin s. These results indicate that activation of the PNS during the absorptive phase of meals contributes significantly to the postprandial insulin secret ory response.