Cell Reports (Apr 2018)

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

  • 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

Journal volume & issue
Vol. 23, no. 4
pp. 967 – 973

Abstract

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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