Hypothalamic glucagon signals through the KATP channels to regulate glucose production

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-...

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Bibliographic Details
Published in:Molecular metabolism (Germany) 2014-04, Vol.3 (2), p.202-208
Main Authors: Abraham, Mona A, Yue, Jessica T.Y, LaPierre, Mary P, Rutter, Guy A, Light, Peter E, Filippi, Beatrice M, Lam, Tony K.T
Format: Article
Language:English
Subjects:
Brief Communication
Endocrinology & Metabolism
Glucagon
Glucose production
Hypothalamus
KATP channels
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Summary: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.
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2013.11.007