G-protein-coupled receptor GPR21 knockout mice display improved glucose tolerance and increased insulin response

Biochem Biophys Res Commun. 2012 Feb 3;418(1):1-5. doi: 10.1016/j.bbrc.2011.11.117. Epub 2011 Dec 1.


GPR21 is an orphan G-protein-coupled receptor. We found that mice deficient for the GPR21 gene were resistant to diet-induced obesity. Knockout mice were leaner than their wildtype counterpart, despite that no difference was observed in food intake. No differences were observed in the respiratory exchange rate and thermogenesis. However, knockout mice were more active than wildtype littermates, and this level of activity may be an underlying reason for the difference in energy balance. Mutant mice were more sensitive to insulin than their wildtype control and showed an improved glucose tolerance. Several inflammatory markers MCP-1, CRP and IP-10 were decreased in mutant animals, suggesting that GPR21 may also mediate its effect through anti-inflammatory mechanisms. We found that GPR21 is widely expressed in all tissues, with the highest levels found in the brain and in the spleen. Overall, these findings suggest that GPR21 may play an important role in regulating body weight and glucose metabolism.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Body Weight / genetics
  • C-Reactive Protein / metabolism
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL10 / metabolism
  • Diet / adverse effects
  • Gene Expression
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Insulin / pharmacology*
  • Insulin Resistance / genetics*
  • Mice
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Tissue Distribution


  • Biomarkers
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chemokine CXCL10
  • GPR21 protein, mouse
  • Insulin
  • Receptors, G-Protein-Coupled
  • C-Reactive Protein
  • Glucose