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Limitations of our study include that delineation of the mechanisms underlying improvement of systems metabolism by GLP-1GIPLani is challenging, not only because mice with germline deletion of PPAR or PPAR are embryonically lethal 28,29,50 , but also because targeting of both incretin receptors along with PPAR, PPAR or PPAR using conditional triple, quadruple or quintuple-knockout mice is beyond the possibilities of most scientific laboratories