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, Raghu Mirmira, Maureen Gannon, Brian T. Layden

Research output: Contribution to journalArticle

11 Citations (Scopus)

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

Fingerprint

Nonesterified Fatty Acids
Cell Survival
G-Protein-Coupled Receptors
Cell Proliferation
Food
Volatile Fatty Acids
Insulin Resistance
Acetates
Cell Death
Maintenance
Parturition
Growth

ASJC Scopus subject areas

  • General

Cite this

Villa, S. R., Priyadarshini, M., Fuller, M. H., Bhardwaj, T., Brodsky, M. R., Angueira, A. R., ... Layden, B. T. (2016). Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. Scientific Reports, 6, [28159]. https://doi.org/10.1038/srep28159

Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. / Villa, Stephanie R.; Priyadarshini, Medha; Fuller, Miles H.; Bhardwaj, Tanya; Brodsky, Michael R.; Angueira, Anthony R.; Mosser, Rockann E.; Carboneau, Bethany A.; Tersey, Sarah A.; Mancebo, Helena; Gilchrist, Annette; Mirmira, Raghu; Gannon, Maureen; Layden, Brian T.

In: Scientific Reports, Vol. 6, 28159, 21.06.2016.

Research output: Contribution to journalArticle

Villa, SR, Priyadarshini, M, Fuller, MH, Bhardwaj, T, Brodsky, MR, Angueira, AR, Mosser, RE, Carboneau, BA, Tersey, SA, Mancebo, H, Gilchrist, A, Mirmira, R, Gannon, M & Layden, BT 2016, 'Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival', Scientific Reports, vol. 6, 28159. https://doi.org/10.1038/srep28159
Villa SR, Priyadarshini M, Fuller MH, Bhardwaj T, Brodsky MR, Angueira AR et al. Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. Scientific Reports. 2016 Jun 21;6. 28159. https://doi.org/10.1038/srep28159
Villa, Stephanie R. ; Priyadarshini, Medha ; Fuller, Miles H. ; Bhardwaj, Tanya ; Brodsky, Michael R. ; Angueira, Anthony R. ; Mosser, Rockann E. ; Carboneau, Bethany A. ; Tersey, Sarah A. ; Mancebo, Helena ; Gilchrist, Annette ; Mirmira, Raghu ; Gannon, Maureen ; Layden, Brian T. / Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival. In: Scientific Reports. 2016 ; Vol. 6.
@article{64037955be364bd081f558d4cbaadfd5,
title = "Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival",
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 {\^a} '/{\^a} ' 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.",
author = "Villa, {Stephanie R.} and Medha Priyadarshini and Fuller, {Miles H.} and Tanya Bhardwaj and Brodsky, {Michael R.} and Angueira, {Anthony R.} and Mosser, {Rockann E.} and Carboneau, {Bethany A.} and Tersey, {Sarah A.} and Helena Mancebo and Annette Gilchrist and Raghu Mirmira and Maureen Gannon and Layden, {Brian T.}",
year = "2016",
month = "6",
day = "21",
doi = "10.1038/srep28159",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival

AU - Villa, Stephanie R.

AU - Priyadarshini, Medha

AU - Fuller, Miles H.

AU - Bhardwaj, Tanya

AU - Brodsky, Michael R.

AU - Angueira, Anthony R.

AU - Mosser, Rockann E.

AU - Carboneau, Bethany A.

AU - Tersey, Sarah A.

AU - Mancebo, Helena

AU - Gilchrist, Annette

AU - Mirmira, Raghu

AU - Gannon, Maureen

AU - Layden, Brian T.

PY - 2016/6/21

Y1 - 2016/6/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84975789637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975789637&partnerID=8YFLogxK

U2 - 10.1038/srep28159

DO - 10.1038/srep28159

M3 - Article

C2 - 27324831

AN - SCOPUS:84975789637

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 28159

ER -