Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion

Chien Ting Wu, Keren I. Hilgendorf, Romina J. Bevacqua, Yan Hang, Janos Demeter, Seung K. Kim, Peter K. Jackson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Multiple G protein-coupled receptors (GPCRs) are expressed in pancreatic islet cells, but the majority have unknown functions. We observed specific GPCRs localized to primary cilia, a prominent signaling organelle, in pancreatic a and B cells. Loss of cilia disrupts B-cell endocrine function, but the molecular drivers are unknown. Using functional expression, we identified multiple GPCRs localized to cilia in mouse and human islet a and B cells, including FFAR4, PTGER4, ADRB2, KISS1R, and P2RY14. Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate ciliary cAMP signaling and promote glucagon and insulin secretion by a-and B-cell lines and by mouse and human islets. Transport of GPCRs to primary cilia requires TULP3, whose knockdown in primary human and mouse islets relocalized ciliary FFAR4 and PTGER4 and impaired regulated glucagon or insulin secretion, without affecting ciliary structure. Our findings provide index evidence that regulated hormone secretion by islet a and B cells is controlled by ciliary GPCRs providing new targets for diabetes.

Original languageEnglish (US)
Pages (from-to)1243-1255
Number of pages13
JournalGenes and Development
Issue number17-18
StatePublished - Sep 1 2021
Externally publishedYes


  • A cells
  • B cells
  • Cilia
  • Diabetes
  • Glucagon
  • Glucose-stimulated insulin secretion
  • Insulin
  • Obesity
  • Pancreas

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


Dive into the research topics of 'Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion'. Together they form a unique fingerprint.

Cite this