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Transcript
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