SCFA Receptors in Pancreatic β Cells: Novel Diabetes Targets?
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.
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Medha
M
Priyadarshini
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Barton
B
Wicksteed
Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208, USA; Department of Pharmacology, Northwestern University, Chicago, IL 60611, USA.
Gary E
GE
Schiltz
Midwestern University Department of Pharmaceutical Sciences, Downers Grove, IL 60515, USA.
Annette
A
Gilchrist
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA. Electronic address: b-layden@northwestern.edu.
Brian T
BT
Layden
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled
FFA2; FFA3; gut microbiota; insulin secretion; short chain fatty acids; β cell mass