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 reduced peptide bond, represents neurotensin agonist. The present study assessed actions JMV-449 on pancreatic beta-cells alone, in combination GIP GLP-1. Further studies examined impact incretin mimetics glucose homeostasis appetite control mice. was resistant to plasma enzyme degradation induced noticeable dose-dependent insulin-releasing BRIN-BD11 beta-cells. In either or GLP-1, augmented (P < 0.05) both hormones, as well enhancing 0.001) insulin secretory activity peptides. also increased beta-cell proliferation significant benefits survival response cytokine-induced apoptosis. (25 nmol/kg) inhibited 0.05–P food intake overnight fasted lean mice, enhanced 0.01) supressing effects an enzymatically stable GLP-1 mimetic. When injected co-jointly glucose, evoked lowering actions, but more interestingly significantly established long-acting mimetics. terms glucose-induced secretion, only signalling associated increases concentrations, this not by JMV-449. is agonist that positively key aspects biological action profile These observations emphasise the, yet untapped, therapeutic potential combined for diabetes.