{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:45:15Z","timestamp":1792496715405,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005277","name":"Presbyterian Historical Society","doi-asserted-by":"publisher","award":["R01DK101991"],"award-info":[{"award-number":["R01DK101991"]}],"id":[{"id":"10.13039\/100005277","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glucagon\u2010like peptide\u20101 (<jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101) is a product of proglucagon cleavage synthesized in L\u00a0cells in the intestinal mucosa, \u03b1\u2010cells in the pancreatic islet, and neurons in the nucleus of the solitary tract. <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 is essential for normal glucose tolerance and acts through a specific <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 receptor that is expressed by islet \u03b2\u2010cells as well as other cell types. Because plasma concentrations of <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 increase following meal ingestion it has been generally presumed that <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 acts as a hormone, communicating information from the intestine to the endocrine pancreas through the circulation. However, there are a number of problems with this model including low circulating concentrations of <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 in plasma, limited changes after meal ingestion and rapid metabolism in the plasma. Moreover, antagonism of systemic <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 action impairs insulin secretion in the fasting state, suggesting that the <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101r is active even when plasma <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 levels are low and unchanging. Consistent with these observations, deletion of the <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101r from islet \u03b2\u2010cells causes intolerance after <jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> glucose, challenges that do not induce <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 secretion. Taken together, these data support a model whereby <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 acts through neural or paracrine mechanisms to regulate physiologic insulin secretion. In contrast, bariatric surgery seems to be a condition in which circulating <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 could have an endocrine effect. Both gastric bypass and sleeve gastrectomy are associated with substantial increases in postprandial <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 release and in these conditions interference with <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101r signaling has a significant impact on glucose regulation after eating. Thus, with either bariatric surgery or treatment with long\u2010acting <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101r agonists, circulating peptide mediates insulinotropic activity. Overall, a case can be made that physiologic actions of <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 are not hormonal, but that an endocrine mechanism of <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101r activation can be co\u2010opted for therapeutics.<\/jats:p>","DOI":"10.1111\/jdi.12466","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T00:47:51Z","timestamp":1458348471000},"page":"50-55","source":"Crossref","is-referenced-by-count":126,"title":["Is <scp>GLP<\/scp>\u20101 a hormone: Whether and When?"],"prefix":"10.1111","volume":"7","author":[{"given":"David","family":"D'Alessio","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism and Nutrition Duke University Medical Center Durham North Carolina 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