GPR142 prompts glucagon-like Peptide-1 release from islets to improve β cell function

Area of Science:

• Endocrinology
• Molecular Biology
• Diabetes Research

Background:

• G protein-coupled receptor 142 (GPR142) agonists are investigated for type 2 diabetes due to insulin-stimulating properties.
• The precise roles of GPR142 within pancreatic islets beyond insulin secretion remain largely unexplored.

Purpose of the Study:

• To investigate the broader functions of GPR142 in pancreatic islet cells.
• To elucidate the mechanisms underlying GPR142's effects on islet cell function and survival.

Main Methods:

• In situ hybridization and immunostaining to determine GPR142 expression patterns in pancreatic islets.
• Treatment of human and mouse islets with a selective GPR142 agonist.
• Assessment of glucagon and insulin secretion, prohormone convertase 1/3 (PC1/3) expression, and beta cell proliferation and apoptosis.

Main Results:

• GPR142 is expressed in both alpha (α) and beta (β) cells.
• GPR142 stimulation increases glucagon secretion and enhances glucagon-like peptide-1 (GLP-1) production and release via PC1/3 upregulation.
• GPR142-mediated insulin secretion and content increase depend on intact GLP-1 receptor signaling; GPR142 also promotes β cell proliferation and protects islets from apoptosis.

Conclusions:

• Local GLP-1 release from α cells is a key mediator of GPR142's beneficial effects on β cell function and mass.
• GPR142 agonism demonstrates potential for treating type 2 diabetes through improved β cell function and survival.
• GPR142 activation offers a promising therapeutic strategy for type 2 diabetes management.