GPR92 activation in islet macrophages controls β cell function in a diet-induced obesity model.

Journal Article (Journal Article)

The molecular mechanisms underlying obesity-induced increases in β cell mass and the resulting β cell dysfunction need to be elucidated further. Our study revealed that GPR92, expressed in islet macrophages, is modulated by dietary interventions in metabolic tissues. Therefore, we aimed to define the role of GPR92 in islet inflammation by using a high-fat diet-induced (HFD-induced) obese mouse model. GPR92-KO mice exhibited glucose intolerance and reduced insulin levels - despite the enlarged pancreatic islets - as well as increased islet macrophage content and inflammation level compared with WT mice. These results indicate that the lack of GPR92 in islet macrophages can cause β cell dysfunction, leading to disrupted glucose homeostasis. Alternatively, stimulation with the GPR92 agonist farnesyl pyrophosphate results in the inhibition of HFD-induced islet inflammation and increased insulin secretion in WT mice, but not in GPR92-KO mice. Thus, our study suggests that GPR92 can be a potential target to alleviate β cell dysfunction via the inhibition of islet inflammation associated with the progression of diabetes.

Full Text

Duke Authors

Cited Authors

  • de Souza, CO; Paschoal, VA; Sun, X; Vishvanath, L; Zhang, Q; Shao, M; Onodera, T; Chen, S; Joffin, N; Bueno, LM; Gupta, RK; Oh, DY

Published Date

  • November 1, 2022

Published In

Volume / Issue

  • 132 / 21

PubMed ID

  • 36066975

Pubmed Central ID

  • PMC9621135

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI160097


  • eng

Conference Location

  • United States