Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control

Neurotensin receptor activation augments the biosctivity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). JMV-449, a C-terminal neurotensin-like fragment with a reduced peptide bond, represents a neurotensin receptor agonist. The present study assessed the a...

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Published in:Biochimica et biophysica acta. General subjects 2021-08, Vol.1865 (8), p.129917-129917, Article 129917
Main Authors: Craig, S.L., Gault, V.A., Shiels, C.E., Hamscher, G., Irwin, N.
Format: Article
Language:English
Subjects:
GIP
GLP-1
Insulin secretion
JMV-449
Neurotensin
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Summary:Neurotensin receptor activation augments the biosctivity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). JMV-449, a C-terminal neurotensin-like fragment with a reduced peptide bond, represents a neurotensin receptor agonist. The present study assessed the actions of JMV-449 on pancreatic beta-cells alone, and in combination with GIP and GLP-1. Further studies examined the impact of JMV-449 and incretin mimetics on glucose homeostasis and appetite control in mice. JMV-449 was resistant to plasma enzyme degradation and induced noticeable dose-dependent insulin-releasing actions in BRIN-BD11 beta-cells. In combination with either GIP or GLP-1, JMV-449 augmented (P 
ISSN:0304-4165
1872-8006
DOI:10.1016/j.bbagen.2021.129917