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However, it should also be recognized that it may be difficult to definitively demonstrate whether DPP-4 does play a physiologically relevant role in cleaving some endogenous substrates in vivo because it can be difficult to distinguish between the intact substrate and the truncated metabolite (because assays are not specific or sensitive enough) and/or because it may be difficult to obtain appropriate samples (e.g., from synapses [neurotransmitters] or interstitial fluid [paracrine signallers])

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