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Dual Incretin Signaling# GLP-1R activation : Enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, reduces appetite via hypothalamic signaling GIPR activation : Potentiates insulin secretion, may improve lipid metabolism and fat distribution, enhances central appetite regulation Synergistic effects : The combination produces greater glycemic and weight effects than either pathway alone Pharmacokinetics# The C20 fatty diacid modification enables albumin binding, yielding a half-life of approximately 5 days and supporting once-weekly administration

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The mice were subsequently euthanized by cervical dislocation and immediately perfused via the right ventricle with 30 ml ice-cold phosphate buffered saline (PBS, pH = 7.4) containing 10 mM N-Ethylmaleimide (NEM, Thermo Fisher Scientific, #23030) to alkylate the free protein thiols, and tissue (liver, heart, lung, and brain) and aorta were carefully dissected