SCFA Receptors in Pancreatic β Cells: Novel Diabetes Targets?

Trends Endocrinol Metab. 2016 Sep;27(9):653-664. doi: 10.1016/j.tem.2016.03.011. Epub 2016 Apr 15.


Nutrient sensing receptors are key metabolic mediators of responses to dietary and endogenously derived nutrients. These receptors are largely G-protein-coupled receptors (GPCRs) and many are gaining significant interest as drug targets with a potential therapeutic role in metabolic diseases. A distinct subclass of nutrient sensing GPCRs, two short chain fatty acid (SCFA) receptors (FFA2 and FFA3) are uniquely responsive to gut microbiota derived nutrients (such as acetate, propionate, and butyrate). Pharmacological, molecular, and genetic studies have investigated their role in organismal glucose metabolism and recently in pancreatic β cell biology. Here, we summarize the present knowledge on the role of these receptors as metabolic sensors in β cell function and physiology, revealing new therapeutic opportunities for type 2 diabetes.

Keywords: FFA2; FFA3; gut microbiota; insulin secretion; short chain fatty acids; β cell mass.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism*
  • Gastrointestinal Microbiome / physiology
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Receptors, G-Protein-Coupled / metabolism


  • Receptors, G-Protein-Coupled