Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats

• DOI: 10.2337/db09-1398
• Publication Date: 2010-04-01T03:55:07Z
• Authors: Chun-Xia Yi; Ning Sun; Mariette T. Acker...; Anneke Alkemade; Ewout Foppen; Jing Shi; Mireille J. Serlie; Ruud M. Buijs; Eric Fliers; Andries Kalsbeek
• Keywords: Sympathetic nervous system

OBJECTIVE The unraveling of the elaborate brain networks that control glucose metabolism presents one current challenges in diabetes research. Within central nervous system, hypothalamus is regarded as key area to regulate energy homeostasis. aim present study was investigate hypothalamic mechanism involved hyperglycemic effects neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). RESEARCH DESIGN AND METHODS Endogenous production (EGP) determined during intracerebroventricular infusions PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. specificity receptors examined by coinfusions antagonists. possible neuronal pathway investigated 1) local injections nuclei, 2) retrograde tracing from thoracic spinal cord preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic parasympathetic denervation block autonomic input liver. RESULTS Intracerebroventricular infusion PACAP-38 increased EGP a similar extent VIP/PACAP-2 (VPAC2) agonist, administration VIP had significantly less influence on EGP. induced increase suppressed preinfusion VPAC2 but not PAC1 antagonist, well denervation. In hypothalamus, immunoreactivity colocalized within paraventricular nuclei projecting preganglionic cord. Local directly into PVN significant CONCLUSIONS This demonstrates signaling via located nucleus an important component production.