Glucagon-like peptide-1 drives energy metabolism on the synaptic highway

FEBS J. 2016 Dec;283(24):4413-4423. doi: 10.1111/febs.13785. Epub 2016 Jul 1.

Abstract

Glucagon-like peptide-1 (GLP-1), a gut-brain hormone, coordinates energy balance in both peripheral organs and the central nervous system (CNS). In the pancreas, GLP-1 facilitates insulin exocytosis or suppresses glucagon exocytosis via multiple pathways such as regulating KATP /Kv channels, N-type Ca2+ channels, and the readily releasable pool. In the CNS, GLP-1 signaling regulates neuronal excitability in various brain regions, including neurons in the hippocampus, hypothalamus, and mesolimbic systems. GLP-1 modulation on synaptic transmission includes both pre- and postsynaptic pathways that are either excitatory or inhibitory. Synaptic transmission conveys information flow in the brain and governs brain-mediated behaviors. The study of GLP-1 control of energy metabolism at a synaptic level may shed light on the role of GLP-1 function in the brain. Various challenges remain including defining the mechanism of GLP-1 release in the brain.

Keywords: GPCR; diabetes; energy metabolism; glucagon-like peptide-1; synaptic transmission.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Calcium / metabolism
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Glucagon-Like Peptide 1 / pharmacology*
  • Humans
  • Incretins / pharmacology
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology

Substances

  • Incretins
  • Glucagon-Like Peptide 1
  • Calcium