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Islet primary cilia motility controls insulin secretion.

Jung Hoon Cho1, Zipeng A Li1, Lifei Zhu1

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Primary cilia in pancreatic islets move, a function essential for glucose-stimulated insulin secretion. This discovery redefines primary cilia as dynamic sensory and motile organelles crucial for beta cell function and diabetes regulation.

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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.