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The inability of the multi-agonists to restore gonadal function in PWA mice is likely due to chronic exposure to fixed concentrations of the exogenous androgen, DHT, which may limit the eventual beneficial effects of the compounds at the gonadal level, even when substantial metabolic improvements are achieved
However, in another study, colesevelam alone or co-administered with CDCA does not have an acute effect on GLP-1 secretion in humans with or without diabetes [179]
Given the limited genetic proxies of GLP-1R-based agonists, MR-PRESSO was not an appropriate approach to sensitivity analysis
These studies indicate that GLP-1 modulates the release of several neurotransmitters including serotonin, dopamine, GABA, and glutamate, which may regulate depressive-like behaviors
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