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H-A GLP-1(7-36)NH2 H-A GLP-1(9-36)NH2 + DPP IV cleavage site of DPP-IV H A E G T F T S D V S S Y L E G Q A A K E F I A W L V K G R P S S G A P P P S H G E G T F T S D L S K Q M E E E A V R L F I E W L K N G G GLP-1(7-36)NH2 Exendin-4 Metabolism of GLP-1 by DPP-4 GLP-1/saline infusion GLP-1(9-36)NH2 and insulin secretion Vahl et al., JCEM 2003 Actions of GLP-1 that Regulate Blood Glucose Concentrations Stimulate -cell function - insulin secretion/synthesis - cell growth/antiapoptosis Inhibit glucagon release Delay gastric emptying Diminish food intake Extrapancreatic effects on glucose - promote glucose uptake - suppress HGP Interruption of GLP-1r signaling causes glucose intolerance Scrocchi et al Nature Med, 1996 DAlessio et al JCI, 1996 Edwards et al Diabetes, 1999 Incretin effect of GLP-1 in healthy humans Glucose GIR Insulin C-peptide M Salehi et al, JCEM, 2008 Effects of GLP-1r blockade on meal-induced glucagon release and gastric emptying Glucagon Gastric Emptying M Salehi, JCEM 2008