Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival

Stephanie R. Villa, Medha Priyadarshini, Miles H. Fuller, Tanya Bhardwaj, Michael R. Brodsky, Anthony R. Angueira, Rockann E. Mosser, Bethany A. Carboneau, Sarah A. Tersey, Helena Mancebo, Annette Gilchrist, Raghavendra G. Mirmira, Maureen Gannon, Brian T. Layden

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs, and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate. Recent studies of FFA2 suggest that it may act as a regulator of β cell function. Here, we set out to explore what role FFA2 may play in regulation of β cell mass. Interestingly, Ffar2 â '/â ' mice exhibit diminished β cell mass at birth and throughout adulthood, and increased β cell death at adolescent time points, suggesting a role for FFA2 in establishment and maintenance of β cell mass. Additionally, activation of FFA2 with Gα q/11-biased agonists substantially increased β cell proliferation in in vitro and ex vivo proliferation assays. Collectively, these data suggest that FFA2 may be a novel therapeutic target to stimulate β cell growth and proliferation.

Original languageEnglish (US)
Article number28159
JournalScientific reports
Volume6
DOIs
StatePublished - Jun 21 2016

ASJC Scopus subject areas

  • General

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