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Updated: Oct 27, 2025

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Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation

Caterina Iorio1, Jillian L Rourke1,2, Lisa Wells1

  • 1Sunnybrook Research Institute, Toronto, Canada.

Communications Biology
|July 24, 2021
PubMed

Insights

Researchers identified a new pathway to regenerate pancreatic beta cells, crucial for treating type 1 diabetes. Silencing G-protein coupled receptor 3 (GPR3) promotes beta cell proliferation and function.

Area of Science:

  • Endocrinology and Metabolism
  • Cell Biology
  • Diabetes Research

Background:

  • Type 1 diabetes is characterized by the loss of pancreatic beta cells, necessitating insulin therapy.
  • Current regenerative therapies face challenges including immune rejection and the need for immunosuppression.

Purpose of the Study:

  • To identify novel pathways regulating adult human beta cell quiescence.
  • To explore therapeutic targets for stimulating beta cell regeneration.

Main Methods:

  • Development of a high-throughput RNA interference (RNAi) screen targeting the GPCRome.
  • Investigation of the G-protein coupled receptor 3 (GPR3) and its downstream effects.

Main Results:

  • Silencing GPR3 induced proliferation of human pancreatic beta cells.
  • GPR3 loss activated Salt Inducible Kinase 2 (SIK2), driving cell cycle entry and increasing beta cell mass.
  • SIK2 activation enhanced insulin secretion in mouse models.

Conclusions:

  • The GPR3-SIK2 pathway is a critical regulator of beta cell mass and function.
  • Targeting this pathway offers a potential strategy for stimulating beta cell regeneration in diabetes.

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