Genes Dev: Ciliary G protein-coupled receptors regulate the secretion of insulin and glucagon

Background: Type 2 diabetes (T2D) is an epidemic disease that affects more than 400 million patients worldwide
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Features of T2D include elevated blood glucose levels, insufficient circulating insulin, and hyperglucagon

Elevated blood glucose levels, insufficient circulating insulin, and hyperglucagon levels.

Results: Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate cilia cAMP signaling and promote the secretion of glucagon and insulin in α and β cell lines and mouse and human pancreatic islets
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TULP3 is required for GPCRs to be transported to primary cilia.

Figure 1 Ciliated GPCRs agonists promote GSIS and GSGS
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The response of MIN6(A) and α-TC9(B) cells to glucose was dose-dependent

Figure 1 Ciliated GPCRs agonists promote GSIS and GSGS

Figure 2 FFAR4 and PTGER4 are ciliated GPCRs expressed by mouse and human pancreatic α and β cells
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(A, B) α, β, and δ cell cilia in mouse (A) and human (B) pancreatic islets

Figure 2 FFAR4 and PTGER4 are ciliated GPCRs expressed by mouse and human pancreatic α and β cells

Figure 3 GSIS and GSGS regulated by FFAR4 are cilia-dependent in pancreatic islets
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GSIS (A, E) and GSGS (C, G) in Tulp3 knockout (ShTulp3) mice (A, C) and human (E, G) pseudo-islets compared with shuffle control (ShCon) mice (A, C) ) There is no change compared with people (E, G)

Figure 3 GSIS and GSGS regulated by FFAR4 are cilia-dependent in pancreatic islets

Our findings provide indicator evidence that the secretion of hormones regulated by pancreatic islet α and β cells is controlled by cilia GPCRs, providing a new target for diabetes

Wu CT, Hilgendorf KI, Bevacqua RJ, et al.

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