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Submitted on September 15, 2005
Accepted on March 1, 2006
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Veterans Affairs Puget Sound Health Care System, Seattle WA 98108 and University of Washington, Seattle WA 98195
* To whom correspondence should be addressed. E-mail: mundin{at}u.washington.edu.
The hormone ghrelin is secreted mainly from the gut, rises in peripheral plasma before meals and is implicated in stimulating hunger, initiating meals and developing obesity. We hypothesize that activation of the sympathetic nervous system contributes to preprandial ghrelin surges. The present studies in isoflurane-anesthetized Wistar rats were designed to determine if sympathetic nerves and neurohormones are capable of stimulating ghrelin secretion. We activated gut sympathetic nerves by two methods: electrical sympathetic nerve stimulation (SNS) and chemical sympathetic nerve activation with intravenous tyramine (TYR) administration. Portal venous blood was sampled before and during a ten-minute sympathetic stimulation. Successful activation of gut sympathetic nerves was verified by increments in portal venous norepinephrine. SNS increased portal ghrelin by +206 ± 50%. In contrast, simply isolating gut sympathetic nerves without applying current had a minimal effect on ghrelin levels. TYR also increased portal ghrelin (
= +52 ± 11%), while saline infusion had little effect. We next sought to determine if the neural stimulation of ghrelin secretion was mediated indirectly via the suppression of insulin secretion seen during SNS and TYR. Streptozotocin-induced diabetes prevented a fall of insulin during TYR, yet the portal ghrelin response ( = +47 ± 18%) was similar to that in non-diabetic rats. Lastly, to test for humoral stimulation of ghrelin, we infused the sympathetic neurohormone, epinephrine, to achieve levels seen during severe stress. Epinephrine failed to stimulate ghrelin secretion ( = +4 ± 35%). We conclude that the neural, but not neurohumoral, branch of the sympathetic nervous system can directly stimulate ghrelin secretion.
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