semaglutide vs placebo versus in individuals with poor weight loss after bariatric surgery: a double-blinded, randomized, placebo-controlled trial Forest plot of semaglutide 2.4

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GIP receptor agonism: Enhances insulin sensitivity and may contribute to improved lipid metabolism

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E N D Presentation Transcript INCRETINS Glucagon-like Peptide 1 (GLP-1)and Glucose-Dependent Insulinotrophic Polypeptide (GIP) account for ~90% of the incretin effect In response to equivalent hyperglycemic stimuli, ORAL glucose elicits a greater insulin response than IV glucose Insulin Glucose-Stimulated Secretion of Insulin Glucose GLUT2 Pancreatic Cell SUR Glucose Potassium channel GK K+ Pyruvate GLP-1 ATP + ATP GIP TCA Cycle* AC + Calcium channel cAMP [Ca2+] Amplifying Triggering AC = adenylyl cyclase

doi: 10.1016/j.isci.2021.103382

Constitutively active form of GPCR increases the chance of phosphorylation by G protein-coupled receptor kinases (GRKs) or other kinases (cAMP-dependent PKA and lipid signaling-activated PKC), and facilitates the binding of -arrestin to the phosphorylated receptor, blocking G protein interaction with a receptor [2224]