Islet primary cilia motility controls insulin secretion.

Area of Science:

• Cell Biology
• Endocrinology
• Physiology

Background:

• Primary cilia are traditionally viewed as static sensory organelles.
• Their role in motility and metabolic regulation is largely unexplored.
• The function of primary cilia in pancreatic beta cells remains unclear.

Purpose of the Study:

• To investigate the motility of primary cilia in pancreatic islets.
• To determine the role of primary cilia movement in glucose-dependent insulin secretion.
• To explore the implications of ciliary function and dysfunction in type 2 diabetes.

Main Methods:

• Microscopy and live-cell imaging of primary cilia in human and mouse pancreatic islets.
• Biochemical assays to identify motor proteins and assess ATP/glucose dependence.
• Functional assays measuring beta cell calcium influx and insulin secretion.
• Analysis of ciliary gene expression in human beta cells and type 2 diabetes.

Main Results:

• Primary cilia in pancreatic islets exhibit active, dynein-driven 3D motion dependent on ATP and glucose metabolism.
• Inhibition of cilia movement impairs beta cell calcium influx and insulin secretion.
• Human beta cells show enriched expression of ciliary genes.
• Alterations in motile cilia genes are observed in type 2 diabetes.

Conclusions:

• Primary cilia possess both sensory and motile functions.
• Pancreatic islet primary cilia movement is critical for regulating insulin secretion.
• These findings redefine primary cilia's role and highlight their importance in metabolic health and type 2 diabetes.