β Cell GLP-1R Signaling Alters α Cell Proglucagon Processing after Vertical Sleeve Gastrectomy in Mice

Autor: Darline Garibay, Jon Lou, Seon A. Lee, Karolina E. Zaborska, Margot H. Weissman, Erica Sloma, Leanne Donahue, Andrew D. Miller, Andrew C. White, M. Dodson Michael, Kyle W. Sloop, Bethany P. Cummings
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cell Reports, Vol 23, Iss 4, Pp 967-973 (2018)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.03.120
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. : 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. Keywords: GLP-1, prohormone convertase 1/3, vertical sleeve gastrectomy, β cell
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