Hypothalamic glucagon signals through the K-ATP channels to regulate glucose production
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Insulin, leptin and GLP-1 signal in the mediobasal hypothalamus (MBH) to lower hepatic glucose production (GP). MBH glucagon action also inhibits GP but the downstream signaling mediators remain largely unknown. In parallel, a lipid-sensing pathway involving MBH AMPK→malonyl-CoA→CPT-1→LCFA-CoA→PKC-δ leading to the activation of KATP channels lowers GP. Given that glucagon signals through the MBH PKA to lower GP, and PKA inhibits AMPK in hypothalamic cell lines, a possibility arises that MBH glucagon-PKA inhibits AMPK, elevates LCFA-CoA levels to activate PKC-δ, and activates KATP channels to lower GP. We here report that neither molecular or chemical activation of MBH AMPK nor inhibition of PKC-δ negated the effect of MBH glucagon. In contrast, molecular and chemical inhibition of MBH KATP channels negated MBH glucagon's effect to lower GP. Thus, MBH glucagon signals through a lipid-sensing independent but KATP channel-dependent pathway to regulate GP.
Date Issued
2014-04-01
Date Acceptance
2013-11-20
Citation
Molecular Metabolism, 2014, 3 (2), pp.202-208
ISSN
2212-8778
Publisher
Elsevier
Start Page
202
End Page
208
Journal / Book Title
Molecular Metabolism
Volume
3
Issue
2
Copyright Statement
© 2013 The Authors. Published by Elsevier GmbH.
Open access under CC BY-NC-ND license.
Open access under CC BY-NC-ND license.
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Hypothalamus
Glucagon
Glucose production
KATP channels
Publication Status
Published