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Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1

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However, dose-dependent gastrointestinal effects limit efficacy, so drugs with GLP-1 and GCG pharmacology can also target alternative pathways and may expand the therapeutic index (132)