Pancreas and Not Gut Mediates the GLP-1-Induced Glucoincretin Effect Joel F. Habener, Violeta Stanojevic  Cell Metabolism  Volume 25, Issue 4, Pages 757-758 (April 2017) DOI: 10.1016/j.cmet.2017.03.020 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 A Model Proposes Local Paracrine Action of the GLP-1/GLP-1R Axis in Both the Pancreas and the Gut In the pancreatic islets, GLP-1 is produced by α cells and acts on GLP-1 receptors on adjacent juxtaposed β cells that induce GSIS. In the gut, GLP-1 secreted locally from enteroendocrine L-cells acts on GLP-1 receptors located on vagal afferent nerve terminals juxtaposed to the L-cells, sending neural pathway signals to the solitary nucleus in the hindbrain. Efferent vagal nerve output is sent to the hypothalamus, stomach, and liver to control food intake, gastric emptying, and hepatic glucose production, respectively. Vagal efferent signaling to the liver is shown as an example. The model further illustrates the presence of the N-terminal diamino-peptidase, Dpp4, which cleaves and inactivates GLP-1, present locally within the tissues at the sites of paracrine GLP-1/GLP-1R signaling in both the pancreatic islets and in the gut. The cleavage of active GLP-1, GLP-1(7-36)amide, results in the production of the receptor-inactive metabolite GLP-1(9-36)amide (GLP-1m), which is secreted into the circulation. Cell Metabolism 2017 25, 757-758DOI: (10.1016/j.cmet.2017.03.020) Copyright © 2017 Elsevier Inc. Terms and Conditions