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Incretin Physiology in Type 2 Diabetes Mellitus Part 2 GLP-1 & GIP Secretion in Type 2 Diabetes Mellitus Postprandial GLP-1 Levels Are Decreased in Patients With IGT and Type 2 Diabetes Glucose-Dependent Insulinotropic Polypeptide (GIP) Response During OGTT What Is DPP-4? • A serine protease widely distributed throughout the body • Cleaves N-terminal amino acids of a number of biologically active peptides, including the incretins GLP-1 and gastric inhibitory peptide (GIP), resulting in inactivation • Its effects on GLP-1 and GIP have been shown to affect incretin activity • Inactivates GLP-1 >50% in ~1 to 2 minutes Ahrën B. Curr Enzyme Inhib. 2005;1:65-73. DPP-4 DPP-4 Action/Inhibition Overview • Discuss normal GLP-1 physiology • Examine the actions of DPP-4 inhibitors and GLP-1R agonists • Review the tissue-specific differences in the mechanisms of action of GLP-1 analogs, DPP-4 inhibitors, and GLP-1R agonists Inhibition of DPP-4 Increases Active GLP-1 Normalization of Diurnal Plasma Glucose Concentrations by Continuous IV GLP-1 Levels of Intact GLP-1 (7-36 amide) Postmeal Are Increased Within the Normal Range After Vildagliptin
