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Only differentially expressed proteins (2.0-fold or 0.5-fold) were excised and subjected to subsequent identification by mass spectrometry (MS) (Bruker Daltonics, Germany)

Neuron 110 , 17881805 e1710 (2022)

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Peripheral effects Via the AMY2 and AMY3 receptors Cagrilintide acts peripherally: Slowing of gastric emptying , stronger than with GLP-1 Suppression of postprandial glucagon , helps control postprandial glycemic spikes Modulation of bone remodeling (via AMY3), a neutral effect, but clinically monitored Synergy with GLP-1 (the mechanistic basis of CagriSema) The main innovation is the complementarity with the GLP-1 pathway : GLP-1 suppresses appetite via the arcuate nucleus of the hypothalamus (POMC neurons, AgRP/NPY inhibition) Amylin suppresses appetite via the area postrema (CGRP-like neurons) Two independent centers, two independent mechanisms