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GLP-1 + GIP + Glucagon Receptor Activation All benefits of GLP-1 activation (appetite, fullness, insulin) GIP enhances insulin response and may reduce GLP-1 side effects Glucagon increases thermogenesis and energy expenditure Combined effect exceeds sum of individual pathways The idea of using glucagon for weight loss was considered counterintuitive until researchers discovered that glucagons metabolic effects depend heavily on the hormonal context

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i , Six residues around the intracellular ionic lock of GLP-1R (H180 2.50b , L251 3.54b , L349 6.40b , S350 6.41b , T353 6.44b and Y402 7.57b ) were selected to calculate the solvent-accessible surface areas (SASA) using the program freeSASA 49

& Deacon, C