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Potentiation of in vitro and in vivo lymphocyte responses
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This multi-receptor activation enables: GLP-1R activation enhances glucose-dependent insulin secretion and reduces appetite through hypothalamic signaling GIPR activation (highest potency: EC50 0.0643 nM) promotes insulin secretion and modulates lipid metabolism GCGR activation (EC50 5.79 nM) increases energy expenditure and promotes hepatic fat oxidation Combined receptor engagement produces dose-dependent reductions in body weight and improvements in glycemic control Research demonstrates that GLP3s balanced activation across three receptors produces superior metabolic effects compared to single or dual agonists, with phase 2 trials showing up to 24.2% weight reduction in 48 weeks[2]
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This was an unexpected result insofar that GPX3 is considered a classical Nrf2-induced gene and TNF- has repeatedly been reported to upregulate other Nrf2 target genes in various cell types including leukocytes of the myeloid lineage, vascular endothelial cells, and osteoblasts 50,51,52,53,54
