The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function

Area of Science:

• Endocrinology
• Molecular Biology
• Genetics

Background:

• Dysregulated glucagon secretion contributes to hyperglycemia and diabetes.
• Understanding pancreatic alpha cell development and function is key for diabetes therapies.

Purpose of the Study:

• To identify pancreatic long non-coding RNAs (lncRNAs) involved in alpha cell function.
• To investigate the role of the Pax6-associated lncRNA Paupar in alpha cell development and glucose homeostasis.

Main Methods:

• Comparative transcriptome analysis of embryonic mouse pancreas and adult mouse islets.
• In vivo studies involving Paupar deletion in mice.
• Analysis of Pax6 splicing and alpha cell gene expression.

Main Results:

• Identified Paupar, a lncRNA enriched in alpha cells, promoting Pax6 alternative splicing.
• Paupar deletion led to dysregulation of Pax6 target genes and alpha cell dysfunction.
• Mice lacking Paupar exhibited blunted glucagon secretion.

Conclusions:

• Paupar plays a critical role in cell-specific regulation of Pax6 for alpha cell function.
• This lncRNA-mediated mechanism is essential for coordinating glucose homeostasis.
• Paupar represents a potential therapeutic target for diabetes treatment.