| First Author | Luo C | Year | 2025 |
| Journal | Adv Sci (Weinh) | Volume | 12 |
| Issue | 41 | Pages | e08858 |
| PubMed ID | 40810739 | Mgi Jnum | J:373684 |
| Mgi Id | MGI:8253008 | Doi | 10.1002/advs.202508858 |
| Citation | Luo C, et al. (2025) Deficiency of Leucine-Rich Repeat Containing G Protein-Coupled Receptor 4 in Pancreas Reduces beta Cell Mass. Adv Sci (Weinh) :e08858 |
| abstractText | Although leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is abundantly expressed in the pancreas, it is currently unknown whether LGR4 impacts pancreatic endocrine cells. Here, a critical role of LGR4 is demonstrated in islet beta cell mass using a group of transgenic mice with LGR4 deficiency. Knock-out of Lgr4 in the pancreas and islet beta cells significantly reduced islet beta cell mass, and subsequently impaired glucose metabolism upon the challenge of a high-fat diet. Deficiency of LGR4 in these mice or in cultured INS-1 cells showed a significant reduction in islet beta cell proliferation measured by Ki-67, EdU, and CCK-8 assay. Increase of islet beta cell proliferation induced by Rspondin-LGR4 signaling occurred via Wnt-beta-catenin-Ccnd1 axis. In addition, the deficiency of LGR4 in islet beta cells significantly increased apoptosis. Inhibition of RANKL-RANK signaling by the TRAF-STOP inhibitor significantly attenuated apoptosis of cultured INS-1 cells induced by deficiency of LGR4. Overall, this work shows that deficiency of LGR4 reduces islet beta cell mass via suppression of proliferation and concurrent increase of apoptosis. LGR4 in pancreatic islets is thus critical for the control of glucose homeostasis. |
