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One possibility is that GLP-1R endocytosis is required for agonist uptake by the brain via hypothalamic tanycytes, as described for leptin 65

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Topical applications deliver the ingredient directly to skin cells, though absorption can be limited by the molecule's size and stability

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[7] [2] By 1986, the major review of the field by Graf and Kastin concluded that the various physiological functions of DSIP and its mechanism of action remain to be established. [2] That sentence was written four decades ago and has not been superseded

Different formulations exist to address specific skin concerns, usage times, and body areas