β Cell GLP-1R Signaling Alters α Cell Proglucagon Processing after Vertical Sleeve Gastrectomy in Mice
| Autor: | Kyle W. Sloop, M. Dodson Michael, Leanne R. Donahue, Karolina E. Zaborska, Darline Garibay, Andrew C. White, Jon Lou, Bethany P. Cummings, Margot H. Weissman, Andrew D. Miller, Seon A. Lee, Erica A. Sloma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system Cell Prohormone convertase Bariatric Surgery Proglucagon General Biochemistry Genetics and Molecular Biology Article Glucagon-Like Peptide-1 Receptor 03 medical and health sciences Paracrine signalling Mice Gastrectomy Insulin-Secreting Cells Paracrine Communication medicine Animals Secretion Receptor lcsh:QH301-705.5 Mice Knockout geography geography.geographical_feature_category Chemistry digestive oral and skin physiology Islet Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Glucagon-Secreting Cells Knockout mouse Proprotein Convertases hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Cell Reports, Vol 23, Iss 4, Pp 967-973 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of type 2 diabetes remission and remarkable increases in postprandial glucagon-like peptide-1 (GLP-1) secretion. GLP-1 plays a critical role in islet function by potentiating glucose-stimulated insulin secretion; however, the mechanisms remain incompletely defined. Therefore, we applied a murine VSG model to an inducible β cell-specific GLP-1 receptor (GLP-1R) knockout mouse model to investigate the role of the β cell GLP-1R in islet function. Our data show that loss of β cell GLP-1R signaling decreases α cell GLP-1 expression after VSG. Furthermore, we find a β cell GLP-1R-dependent increase in α cell expression of the prohormone convertase required for the production of GLP-1 after VSG. Together, the findings herein reveal two concepts. First, our data support a paracrine role for α cell-derived GLP-1 in the metabolic benefits observed after VSG. Second, we have identified a role for the β cell GLP-1R as a regulator of α cell proglucagon processing. In Brief The mechanisms by which GLP-1 enhances insulin secretion remain incompletely defined. Garibay et al. show that β cell GLP-1R signaling regulates α cell PC1/3 expression and GLP-1 production, pointing to an intra-islet paracrine positive feedback loop by which GLP-1-potentiated insulin secretion is amplified. |
| Databáze: | OpenAIRE |
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