PMID- 25597994
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20150218
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 457
IP  - 4
DP  - 2015 Feb 20
TI  - Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 
      hypothalamic neurons.
PG  - 532-7
LID - S0006-291X(15)00038-8 [pii]
LID - 10.1016/j.bbrc.2015.01.016 [doi]
AB  - Insulin signaling in the hypothalamus plays an important role in food intake and 
      glucose homeostasis. Hypothalamic neuronal functions are modulated by glial 
      cells; these form an extensive network connecting the neurons and cerebral 
      vasculature, known as the neurovascular unit (NVU). Brain pericytes are 
      periendothelial accessory structures of the blood-brain barrier and integral 
      members of the NVU. However, the interaction between pericytes and neurons is 
      largely unexplored. Here, we investigate whether brain pericytes could affect 
      hypothalamic neuronal insulin signaling. Our immunohistochemical observations 
      demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting 
      immunoreactivity of platelet-derived growth factor receptor beta (a pericyte 
      marker), and laminin, a basal lamina marker. We then exposed a murine 
      hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from 
      primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but 
      not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the 
      insulin-stimulated phosphorylation of Akt in GT1-7 cells in a 
      concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine 
      phosphorylation of insulin receptor beta without changing its expression or 
      localization in cytosolic or plasma membrane fractions. These results suggest 
      that pericytes, rather than astrocytes, increase insulin sensitivity in 
      hypothalamic neurons by releasing soluble factors under physiological conditions 
      in the NVU.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Takahashi, Hiroyuki
AU  - Takahashi H
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan.
FAU - Takata, Fuyuko
AU  - Takata F
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan; BBB Laboratory, PharmaCo-Cell Co., 
      Ltd., Nagasaki, Japan.
FAU - Matsumoto, Junichi
AU  - Matsumoto J
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan.
FAU - Machida, Takashi
AU  - Machida T
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan.
FAU - Yamauchi, Atsushi
AU  - Yamauchi A
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan.
FAU - Dohgu, Shinya
AU  - Dohgu S
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan.
FAU - Kataoka, Yasufumi
AU  - Kataoka Y
AD  - Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical 
      Sciences, Fukuoka University, Fukuoka, Japan; BBB Laboratory, PharmaCo-Cell Co., 
      Ltd., Nagasaki, Japan. Electronic address: ykataoka@fukuoka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150115
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Insulin)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/*metabolism
MH  - Hypothalamus/blood supply/*cytology
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Mice
MH  - Pericytes/cytology/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Insulin/metabolism
MH  - Receptor, Platelet-Derived Growth Factor beta/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Hypothalamus
OT  - Insulin receptor
OT  - Insulin signaling
OT  - Neuron
OT  - Neurovascular unit
OT  - Pericyte
EDAT- 2015/01/20 06:00
MHDA- 2015/04/18 06:00
CRDT- 2015/01/20 06:00
PHST- 2014/12/22 00:00 [received]
PHST- 2015/01/07 00:00 [accepted]
PHST- 2015/01/20 06:00 [entrez]
PHST- 2015/01/20 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
AID - S0006-291X(15)00038-8 [pii]
AID - 10.1016/j.bbrc.2015.01.016 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2015 Feb 20;457(4):532-7. doi: 
      10.1016/j.bbrc.2015.01.016. Epub 2015 Jan 15.