Format

Send to

Choose Destination
Mol Metab. 2013 Nov 28;3(2):202-8. doi: 10.1016/j.molmet.2013.11.007. eCollection 2014 Apr.

Hypothalamic glucagon signals through the KATP channels to regulate glucose production.

Author information

1
Toronto General Research Institute, University Health Network, Toronto, Canada ; Departments of Physiology, University of Toronto, Toronto, Canada.
2
Toronto General Research Institute, University Health Network, Toronto, Canada ; Departments of Medicine, University of Toronto, Toronto, Canada.
3
Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College of London, South Kensington, London, UK.
4
Department of Pharmacology, University of Alberta, Edmonton, Canada.
5
Toronto General Research Institute, University Health Network, Toronto, Canada ; Departments of Physiology, University of Toronto, Toronto, Canada ; Departments of Medicine, University of Toronto, Toronto, Canada ; Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada.

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.

KEYWORDS:

Glucagon; Glucose production; Hypothalamus; KATP channels

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center