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Glucagon-Like Peptide 1 Stimulates Hypothalamic Proopiomelanocortin Neurons
Glucagon-like peptide 1 activates appetite-controlling neurons in the brain's hypothalamus
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Abstract
GLP-1 increases the electrical activity of POMC neurons by approximately 70% through activation of L-type calcium channels.
- GLP-1 receptor mRNA is densely expressed in the hypothalamic arcuate nucleus, overlapping with POMC neurons.
- Activation of POMC neurons is associated with appetite suppression, while inhibition or lack of POMC-derived peptides can lead to obesity.
- The stimulatory effect of GLP-1 on POMC neurons is mimicked by the GLP-1 receptor agonist exendin-4 and blocked by the receptor antagonist exendin 9-39.
- GLP-1's effect on POMC neurons occurs independently of synaptic inputs, as shown by unchanged responses in the presence of synaptic blockers.
- The increase in Ca2+ currents following GLP-1 application is significantly reduced by L-type Ca2+ channel antagonist nifedipine.
- PKA activation is involved in the effects of GLP-1 on POMC neurons, as indicated by the mimicking effect of forskolin and inhibition by Rp-8-Bromo-cAMPS.
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