Pathophysiologic significance of PACAP in hypothalamus

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kagoshima University
• Principal Investigator: Miyata Atsuro 鹿児島大学, 医歯学域医学系, 教授 (60183969)
• Co-Investigator(Kenkyū-buntansha): INOUE Kazuhiko 鹿児島大学, 医歯学域医学系, 助教 (30363641) ; KAMBE Yuki 鹿児島大学, 医歯学域医学系, 助教 (60549913)
• Co-Investigator(Renkei-kenkyūsha): KATSUURA Goro 鹿児島大学, 医歯学総合研究科, 特任講師 (20401226)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: PACAP / 視床下部 / 摂食

Outline of Final Research Achievements

Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in hypothalamus with highest concentration. To evaluate PACAP function as a hypothalamic factor, we attempted to elucidate the regulatory mechanism of gene expression of PACAP specific receptor, PAC1. Further we tried to evaluate the function of PACAP in appetite control and energy metabolism by using PACAP-knock out (KO) mice. As a result, we found that the expression of PAC1 is negatively regulated by ER stress. As regarding glycogen metabolism, PACAP potentiates not only glycogenolysis but also glycogensesis of astrocytes. In the analysis of PACAP KO mice, their food intake were significantly decreased and the gene expression of PACAP in PACAP KO mice were significantly increased by fasting. During refeeding, the increments of gene expression of NPY and AgRP, orexigenic peptides were cancelled in PACAP KO mice. These suggest orexigenic function of PACAP in appetite control.

Free Research Field

分子薬理学