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The role of GIP and pancreatic GLP-1 in the glucoregulatory effect of DPP-4 inhibition in mice – published online 14/08/2019

Fig from Hutch paper

Chelsea R. Hutch, Karen Roelofs, April Haller, Joyce Sorrell, Kyle Leix, David D. D’Alessio, Robert Augustin, Randy J. Seeley, Thomas Klein, Darleen A. Sandoval

Several effective glucoregulatory pharmaceuticals target incretin peptides, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). One such class of pharmaceuticals prolongs the half-life of these peptides by inhibiting the degradation enzyme, dipeptidyl peptidase-4 (DPP-4). It is commonly thought that the intestinal source of GLP-1 is responsible for improved glucose homeostasis by DPP-4 inhibitors. In this issue, Hutch et al ( studied transgenic mouse models in which GLP-1 is solely expressed in the pancreas or the intestine. Their findings indicate that pancreatic GLP-1 contributes to the effectiveness of DDP-4 inhibitors. In addition, in a mouse model with no GLP-1 production, DPP-4 inhibitors retained a full glucoregulatory effect through the actions of GIP. The authors conclude that these findings suggest that increases in pancreatic GLP-1 and GIP are necessary for the full effect of DPP-4 inhibitors on glucose tolerance in mice.

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