This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by D’Alessio, D. A. Articles by Havel, P. J. Search for Related Content PubMed PubMed Citation Articles by D’Alessio, D. A. Articles by Havel, P. J.

Activation of the Parasympathetic Nervous System Is Necessary for Normal Meal-Induced Insulin Secretion in Rhesus Macaques¹

Department of Medicine, University of Washington (D.D., G.J.T.), and Department of Veterans Affairs Puget Sound Health Care System (G.J.T.), Seattle, Washington 98195; Department of Medicine and Physiology, University of Alberta (T.J.K.), Edmonton, Alberta, Canada AB T6G 252; and Department of Nutrition, University of California (P.J.H.), Davis, California 95616

Address all correspondence and requests for reprints to: David D’Alessio, M.D., Division of Endocrinology and Metabolism, University of Cincinnati, Box 670547, Cincinnati, Ohio 45267-0547. E-mail: david.d'alessio{at}uc.edu

Meal-induced insulin secretion is thought to be regulated primarily by absorbed nutrients and incretin hormones released from the gastrointestinal tract. In addition, the parasympathetic nervous system (PNS) is known to mediate preabsorptive, or cephalic phase, insulin secretion. Despite evidence that the PNS remains activated during the absorptive phase of the meal, its role in mediating postprandial insulin secretion has not been established. To study the role of the PNS in absorptive phase insulin release, we measured 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 trimethaphan (nicotinic blockade). During the infusion of saline, plasma levels of glucose, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 increased promptly after meal ingestion and remained elevated throughout the 60 min of the study. The PP response was nearly abolished in animals treated with trimethaphan, indicating functional blockade of PNS input to the islet, and in contrast to the control study, there were minimal changes in plasma concentrations of glucose, incretin hormones, and insulin. Because trimethaphan inhibited glycemic and incretin stimuli in addition to blocking PNS input to the islet, it was not possible to discern the relative roles of these factors in the stimulation of insulin secretion. Atropine also significantly decreased PNS transmission to the islet, as reflected by PP levels similar to those observed with trimethaphan. Unlike the trimethaphan study, plasma glucose levels rose normally during atropine treatment and were similar to those in the control study over the course of the experiments (114 ± 22 and 132 ± 23 mmol/L·60 min, respectively). In addition, the rise in plasma glucagon-like peptide-1 following the meal was not suppressed by atropine, and the glucose-dependent insulinotropic polypeptide responses were only modestly decreased. 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 than 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 incretins. These results indicate that activation of the PNS during the absorptive phase of meals contributes significantly to the postprandial insulin secretory response.

This article has been cited by other articles:

				T. P. Vahl, D. L. Drazen, R. J. Seeley, D. A. D'Alessio, and S. C. Woods Meal-Anticipatory Glucagon-Like Peptide-1 Secretion in Rats Endocrinology, February 1, 2010; 151(2): 569 - 575. [Abstract] [Full Text] [PDF]

				K. L. Teff Visceral Nerves: Vagal and Sympathetic Innervation JPEN J Parenter Enteral Nutr, September 1, 2008; 32(5): 569 - 571. [Abstract] [Full Text] [PDF]

				C. Maier, M. Riedl, G. Vila, P. Nowotny, M. Wolzt, M. Clodi, B. Ludvik, and A. Luger Cholinergic Regulation of Ghrelin and Peptide YY Release May Be Impaired in Obesity Diabetes, September 1, 2008; 57(9): 2332 - 2340. [Abstract] [Full Text] [PDF]

				J. Rossi, P. Santamaki, M. S. Airaksinen, and K.-H. Herzig Parasympathetic Innervation and Function of Endocrine Pancreas Requires the Glial Cell Line-Derived Factor Family Receptor {alpha}2 (GFR{alpha}2) Diabetes, May 1, 2005; 54(5): 1324 - 1330. [Abstract] [Full Text] [PDF]

				D. E. Johnson, H. Yamazaki, K. M. Ward, A. W. Schmidt, W. S. Lebel, J. L. Treadway, E. M. Gibbs, W. S. Zawalich, and H. Rollema Inhibitory Effects of Antipsychotics on Carbachol-Enhanced Insulin Secretion From Perifused Rat Islets: Role of Muscarinic Antagonism in Antipsychotic-Induced Diabetes and Hyperglycemia Diabetes, May 1, 2005; 54(5): 1552 - 1558. [Abstract] [Full Text] [PDF]

				B. V. de Courten, C. Weyer, N. Stefan, M. Horton, A. DelParigi, P. Havel, C. Bogardus, and P. A. Tataranni Parasympathetic Blockade Attenuates Augmented Pancreatic Polypeptide But Not Insulin Secretion in Pima Indians Diabetes, March 1, 2004; 53(3): 663 - 671. [Abstract] [Full Text] [PDF]

				Y. Anini, T. Hansotia, and P. L. Brubaker Muscarinic Receptors Control Postprandial Release of Glucagon-Like Peptide-1: In Vivo and in Vitro Studies in Rats Endocrinology, June 1, 2002; 143(6): 2420 - 2426. [Abstract] [Full Text] [PDF]

				M. Amstalden, M.R. Garcia, R.L. Stanko, S.E. Nizielski, C.D. Morrison, D.H. Keisler, and G.L. Williams Central Infusion of Recombinant Ovine Leptin Normalizes Plasma Insulin and Stimulates a Novel Hypersecretion of Luteinizing Hormone after Short-Term Fasting in Mature Beef Cows Biol Reprod, May 1, 2002; 66(5): 1555 - 1561. [Abstract] [Full Text]

				P. J. Havel Peripheral Signals Conveying Metabolic Information to the Brain: Short-Term and Long-Term Regulation of Food Intake and Energy Homeostasis Exp Biol Med, December 1, 2001; 226(11): 963 - 977. [Abstract] [Full Text] [PDF]

				P. Gilon and J.-C. Henquin Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic {beta}-Cell Function Endocr. Rev., October 1, 2001; 22(5): 565 - 604. [Abstract] [Full Text] [PDF]