Premium
Insulin and glucose stimulation of vasopressin (VP) and oxytocin (OT) release requires glucokinase (GK) and PI3 kinase (PI3K)
Author(s) -
Sladek Celia D,
Song Zhilin,
Stevens Wanida
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1123.8
Subject(s) - medicine , endocrinology , wortmannin , glut4 , chemistry , diazoxide , stimulation , vasopressin , oxytocin , insulin , glucokinase , glucose transporter , pi3k/akt/mtor pathway , biology , signal transduction , biochemistry
Neurons in the supraoptic nuclei (SON) produce OT and VP and express insulin receptors (InsR) and GK. Since OT is an anorexic agent and GK and InsR are hallmarks of cells that function as ‘metabolic sensors’, we evaluated the effect of glucose, Ins, and their downstream effector, K ATP channels, on OT/VP release from rat hypothalamo‐neurohypophyseal system explants, and the effect of blocking GK and PI3K (mediates Ins‐induced mobilization of glucose transporter, GLUT4) on Ins (3ng/ml) and Ins+glucose‐induced OT/VP release. Ins increased OT/VP release and the response was sustained when glucose was increased from 2 to 6 mM (p≤0.002). The OT/VP responses to Ins+glucose were blocked by the GK inhibitor, alloxan (4mM; p≤0.002), and the PI3K inhibitor, wortmannin (10nM; OT: p=0.03; VP: p≤0.002). Closing of K ATP channels with 200nM glybenclamide increased OT/VP release (OT: p<0.003; VP: p<0.05). These results suggest that Ins activation of PI3K increases GK‐mediated ATP production inducing closure of K ATP channels and stimulation of OT/VP release. The findings are consistent with SON OT/VP neurons functioning as ‘metabolic‐sensors’ to participate in appetite regulation. Supported by NIH R21 HD072428.