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alanine accumulation represses the GAD1 , UGA1 , and UGA2 genes (GABA shunt pathway), which decreases intracellular NADPH [38]

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This could be achieved via a tissue-targeted fusion protein approach with GLP-1-mediated delivery of E2 to tissues with high density of GLP-1Rs—to minimize gynecological effects—through the use of fusion peptides (318, 319) or through novel SERMs that will retain the beneficial metabolic effects of E2 in desired tissues while antagonizing ERs in breast and uterus