Is GLP‐1 a hormone: Whether and When?
| العنوان: | Is GLP‐1 a hormone: Whether and When? |
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| المؤلفون: | David A. D'Alessio |
| المصدر: | Journal of Diabetes Investigation |
| بيانات النشر: | John Wiley and Sons Inc., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, endocrine system, Proceedings of INCRETIN 2015, A Symposium Celebrating the 45th Anniversary of the Discovery of GIP, 29–31 July 2015, Vancouver, Canada. This publication has been supported by: The Local Organizing Committee of INCRETIN 2015, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Mini Review, Incretin, 030209 endocrinology & metabolism, Proglucagon, Incretins, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Animals, Humans, Insulin, Review Articles, geography, geography.geographical_feature_category, business.industry, Insulin secretion, digestive, oral, and skin physiology, General Medicine, Fasting, Islet, Glucagon-like peptide-1, Glucagon‐like peptide‐1, 030104 developmental biology, Postprandial, Endocrinology, Glucagon-Secreting Cells, Blood sugar regulation, business, hormones, hormone substitutes, and hormone antagonists, Hormone |
| الوصف: | Glucagon‐like peptide‐1 (GLP‐1) is a product of proglucagon cleavage synthesized in L cells in the intestinal mucosa, α‐cells in the pancreatic islet, and neurons in the nucleus of the solitary tract. GLP‐1 is essential for normal glucose tolerance and acts through a specific GLP‐1 receptor that is expressed by islet β‐cells as well as other cell types. Because plasma concentrations of GLP‐1 increase following meal ingestion it has been generally presumed that GLP‐1 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 GLP‐1 in plasma, limited changes after meal ingestion and rapid metabolism in the plasma. Moreover, antagonism of systemic GLP‐1 action impairs insulin secretion in the fasting state, suggesting that the GLP‐1r is active even when plasma GLP‐1 levels are low and unchanging. Consistent with these observations, deletion of the GLP‐1r from islet β‐cells causes intolerance after IP or IV glucose, challenges that do not induce GLP‐1 secretion. Taken together, these data support a model whereby GLP‐1 acts through neural or paracrine mechanisms to regulate physiologic insulin secretion. In contrast, bariatric surgery seems to be a condition in which circulating GLP‐1 could have an endocrine effect. Both gastric bypass and sleeve gastrectomy are associated with substantial increases in postprandial GLP‐1 release and in these conditions interference with GLP‐1r signaling has a significant impact on glucose regulation after eating. Thus, with either bariatric surgery or treatment with long‐acting GLP‐1r agonists, circulating peptide mediates insulinotropic activity. Overall, a case can be made that physiologic actions of GLP‐1 are not hormonal, but that an endocrine mechanism of GLP‐1r activation can be co‐opted for therapeutics. |
| اللغة: | English |
| تدمد: | 2040-1124 2040-1116 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06b7024e1ac004df6533654433dfddf5Test http://europepmc.org/articles/PMC4854505Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....06b7024e1ac004df6533654433dfddf5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20401124 20401116 |
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