Tyramine-Mediated Activation of Sympathetic Nerves Inhibits Insulin Secretion in Humans

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 10; pp. 4035 - 4038
• Main Authors: Gilliam, Lisa K., Palmer, Jerry P., Taborsky, Gerald J.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.10.2007; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adolescent; Adult; Arginine - administration & dosage; Beta cells; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Cell activation; Electrical stimuli; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Human subjects; Humans; Hypotheses; Insulin; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Male; Medical sciences; Norepinephrine; Norepinephrine - blood; Physiology; Sympathetic nerves; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Sympathomimetics - administration & dosage; Tyramine; Tyramine - administration & dosage; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Sympathetic nerve; Tyramine; Obesity; Nutrition; Insulin human; Secretion; Nutrition disorder; Metabolic diseases; Activation; Sympathomimetic; Inhibitor; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-0536

Context: Older studies have shown that high doses of norepinephrine infused into human subjects can inhibit insulin secretion. Similar inhibition during electrical stimulation of sympathetic nerves in animals raises the possibility that the suppression of insulin secretion seen in humans could reflect a physiological effect of sympathetic nerves on islet β-cells. However, a direct test of the hypothesis that moderate and selective activation of these nerves is sufficient to inhibit insulin secretion in humans is lacking. Objective: We sought to test this hypothesis by releasing moderate amounts of endogenous norepinephrine selectively from the sympathetic nerves of normal human subjects by infusing them with low doses of the indirect sympathomimetic agent tyramine. Methods: During a single study visit, 11 healthy subjects received iv injections of arginine either alone or in combination with a low-dose tyramine infusion. Physiological (blood pressure) and biochemical (insulin, glucose, and norepinephrine) parameters were measured. Results: The acute insulin response to arginine was significantly reduced during tyramine compared with that seen in the absence of tyramine (P = 0.036). Conclusions: These data suggest that moderate and selective activation of sympathetic nerves inhibits insulin release in humans.