FFAR3 modulates insulin secretion and global gene expression in mouse islets

Area of Science:

• Endocrinology
• Metabolism
• Molecular Biology

Background:

• The free fatty acid receptor-3 (FFAR3) is present in pancreatic beta cells.
• Its precise function in regulating insulin secretion remains unclear.

Purpose of the Study:

• To investigate the role of FFAR3 in insulin secretion.
• To elucidate the signaling pathways involved in FFAR3-mediated regulation of glucose-stimulated insulin secretion.

Main Methods:

• Utilized islets from global FFAR3 knockout (Ffar3(-/-)) and wildtype (WT) mice.
• Assessed glucose-stimulated insulin secretion (GSIS) in isolated islets.
• Performed RNA sequencing to analyze islet transcriptomes.
• Investigated FFAR3 signaling using its ligand (propionate) and a specific agonist.

Main Results:

• Ffar3(-/-) islets exhibited enhanced glucose-dependent insulin secretion compared to WT islets.
• FFAR3 activation, via its ligand or agonist, inhibited GSIS through a Gαi/o pathway.
• RNA sequencing revealed significant alterations in islet gene expression in Ffar3(-/-) mice.

Conclusions:

• FFAR3 signaling negatively regulates glucose-stimulated insulin secretion via a Gαi/o-sensitive pathway.
• FFAR3 deletion impacts the islet transcriptome, suggesting broader roles in beta cell function.
• Further in vivo studies are required to fully define FFAR3's physiological role.