, Volume 48, Issue 4, pp 612-615
Date: 10 Mar 2005

Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors

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Our opponents in this debate, Nauck and El-Ouaghlidi, have challenged the standard view that the therapeutic actions of the dipeptidyl peptidase-IV (DPP-IV) inhibitors are mediated by glucagon-like peptide-1 (GLP-1) [1]. Based on the findings that exogenously administered GLP-1 is rapidly and extensively degraded by DPP-IV [2], and that this degradation appears to be mediated by DPP-IV [3], it was proposed that DPP-IV inhibitors could enhance the survival of intact, biologically active GLP-1 and thus be of use in the treatment of type 2 diabetes mellitus [2, 4]. Although the kinetic studies performed by Mentlein et al. clearly demonstrated that DPP-IV may have substrates in addition to GLP-1 [5, 6], the effect of this enzyme on GLP-1 was considered to be of particular importance because: (1) GLP-1 is extremely susceptible to rapid degradation by DPP-IV, as compared with the majority of other substrates; (2) DPP-IV degradation is the primary route of GLP-1 inactivation; (3) ...

Duality of interest

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