Molecular mechanism for highly sensitive response to peripheral hormones in hypothalamic neurons and homeostatic role

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15182
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Jichi Medical University
• Principal Investigator: Yada TOSHIHIKO 自治医科大学, 医学部, 教授 (60166527)
• Co-Investigator(Renkei-kenkyūsha): MASANORI Nakata 自治医科大学, 医学部, 准教授 (10305120) ; TATSUYA Dezaki 自治医科大学, 医学部, 准教授 (90337329) ; YUSAKU Iwasaki 自治医科大学, 医学部, 講師 (60528420) ; SHIGETOMO Suyama 自治医科大学, 医学部, 助教 (80528414)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: インスリン / 視床下部 / 室傍核 / 神経内分泌 / オキシトシン神経 / PDK１

Outline of Final Research Achievements

Peripheral injection of insulin induced c-Fos in hypothalamic paraventricular nucleus (PVN) particularly in large-sized oxytocin neurons, and increased plasma oxytocin levels in mice. Very low levels of nsulin at picomolar concentrations increased cytosolic free calcium in single neurons isolated from PVN mostly in large-sized neuroendocrine oxytocin neurons. In oxytocin neuron-specific PDK1 knockdown mice via Cre-LoxP system, picomolar insulin failed to activate neuroendocrine oxytocin neurons and peripheral insulin-induced rises in plasma oxytocin disappeared.
These results indicate that large-sized neuroendocrine oxytocin neurons in PVN respond to very low levels of insulin via mechanisms involving PDK1.

Free Research Field

生理学