Biology of Incretins: GLP-1 and GIP Laurie L. Baggio, Daniel J. Drucker  Gastroenterology  Volume 132, Issue 6, Pages 2131-2157 (May 2007) DOI: 10.1053/j.gastro.2007.03.054 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 Structures of (A) the proglucagon gene, (B) mRNA, and (C) protein. (D) Tissue-specific posttranslational processing of proglucagon in the pancreas leads to the generation of Glicentin-related polypeptide (grpp), glucagon (gluc), intervening peptide-1 (ip-1), and major proglucagon fragment (mpgf), whereas glicentin, oxyntomodulin (oxm), intervening peptide-2 (ip-2), and GLP-1 and GLP-2 are liberated after proglucagon processing in the intestine and brain. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 Bioactive GLP-1(7-36)amide and GIP (1-42) are released from the small intestine after meal ingestion and enhance glucose-stimulated insulin secretion (incretin action). DPP-4 rapidly converts GLP-1 and GIP to their inactive metabolites GLP-1 (9-36) and GIP (3-42) in vivo. Inhibition of DPP-4 activity prevents GLP-1 and GIP degradation, thereby enhancing incretin action. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 GLP-1 actions in peripheral tissues. The majority of the effects of GLP-1 are mediated by direct interaction with GLP-1Rs on specific tissues. However, the actions of GLP-1 in liver, fat, and muscle most likely occur through indirect mechanisms. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 GLP-1R–dependent intracellular signal transduction pathways in the pancreatic β-cell. Although there is considerable overlap between pathways, the major effectors that couple GLP-1R activation to insulin secretion and biosynthesis (green), β-cell proliferation and neogenesis (blue), inhibition of apoptosis (red), and ER stress reduction (purple) are highlighted. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 (A) ProGIP gene, (B) mRNA, and (C) protein. Bioactive GIP is generated from its proGIP protein precursor by posttranslational cleavage at single arginine residues that flank GIP. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Figure 6 GIP actions in peripheral tissues. Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions

Daniel J. Drucker, MD Gastroenterology 2007 132, 2131-2157DOI: (10.1053/j.gastro.2007.03.054) Copyright © 2007 AGA Institute Terms and Conditions