title: Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.
abstract: 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 β (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 β 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.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; BBB Laboratory, PharmaCo-Cell Co., Ltd., Nagasaki, Japan.
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Takata
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Machida
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Dohgu
authors.affiliation: 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.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism*; D007031:Hypothalamus / Q000098:blood supply / Q000166:cytology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D020286:Pericytes / Q000166:cytology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017077:Culture Media, Conditioned; D007328:Insulin; D011972:Receptor, Insulin; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Hypothalamus; Insulin receptor; Insulin signaling; Neuron; Neurovascular unit; Pericyte