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Pharmacodynamic Effects and Duration Despite measurable plasma clearance, pharmacodynamic effects extend well beyond plasma half-life[20]: Weight loss effects continue throughout treatment with no plateau observed within 48-week study periods Glycemic improvements persist between weekly doses with stable glucose control Appetite suppression effects remain consistent throughout dosing intervals Tissue receptor occupancy likely exceeds plasma peptide concentrations This disconnect between pharmacokinetics and pharmacodynamics suggests prolonged receptor engagement, tissue depot effects, or persistent downstream signaling cascade activation
Materials and Methods RAW264 Cells, GSH Depletion, and Treatment RAW264 cells were cultured in Roswell Park Memorial Institute medium 1640 with 2 mM l-glutamine (Sigma), 100 U/ml penicillin, 100 g/ml streptomycin sulfate (Invitrogen/Life Technologies), and 10% heat-inactivated FCS (Sigma)-omplete medium
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