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Briefly, the preproglucagon gene undergoes tissue-specific post-translational modification with the help of specific propeptidase convertase (PC1/3) to produce two variants of GLP-1, the amidated GLP-1 [736], and the glycine-extended GLP-1 [737] in the ileum and hypothalamus (Zheng et al., 2024)

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A dual GLP-1-estrogen conjugate (GE) designed to selectively deliver estrogen to GLP-1R + cells induced substantial weight loss in mice without evidence of systemic estrogenic effects, as assessed by uterine weight and growth of estrogen-dependent breast cancer xenografts ( In another preclinical study, GE demonstrated superior metabolic effects compared to GLP-1-GIP or GLP-1-GIP-glucagon multiagonist therapies in models of polycystic ovary syndrome (PCOS), a condition frequently associated with obesity and insulin resistance