Uncoupling protein 2 (UCP2) is a mitochondrial carrier protein that is expressed in pancreatic islets and has been shown to negatively regulate glucose-stimulated insulin secretion.1,2 High levels of UCP2 expression can disrupt pancreatic β cell function and downregulate insulin secretion thereby contributing to the development of type 2 diabetes.3 Genipin, a compound isolated from Gardenis jasminoides Ellis fruits, was originally identified as a protein cross-linking agent. Genipin is a cell-permeable inhibitor of UCP2 activity.4 Genipin, at 5 µM, increases glucose-stimulated insulin secretion in isolated pancreatic islets chronically exposed to high levels of glucose.5 Genipin also exhibits anti-inflammatory and anti-angiogenic properties by inducing apoptosis in FaO rat hepatoma cells and human hepatocarcinoma Hep3B cells.6
1
Chan, C.B., De Leo, D., Joseph, J.W., et al. Increased uncoupling protein-2 levels in b-cells are associated with impaired glucose-stimulated insulin secretion mechanism of action. Diabetes501302-1310(2001).
2
Zhang, C., Baffy, G., Perret, P., et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, b cell dysfunction, and type 2 diabetes. Cell105745-755(2001).
3
Sesti, G., Cardellini, M., Marini, M.A., et al. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. Diabetes521280-1283(2003).
4
Parton, L.E., Ye, C.P., Coppari, R., et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature449228-232(2007).
5
Zhang, C., Parton, L.E., Ye, C.P., et al. Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity-and high glucose-induced b cell dysfunction in isolated pancreatic islets. Cell Metab3417-427(2006).
6
Kim, B., Kim, H., Lee, S., et al. Genipin-induced apoptosis in hepatoma cells is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of mitochondrial pathway. Biochem Pharmacol701398-1407(2005).
Chan, C.B., De Leo, D., Joseph, J.W., et al. Increased uncoupling protein-2 levels in b-cells are associated with impaired glucose-stimulated insulin secretion mechanism of action. Diabetes501302-1310(2001).
Parton, L.E., Ye, C.P., Coppari, R., et al. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature449228-232(2007).
Zhang, C., Parton, L.E., Ye, C.P., et al. Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity-and high glucose-induced b cell dysfunction in isolated pancreatic islets. Cell Metab3417-427(2006).
Kim, B., Kim, H., Lee, S., et al. Genipin-induced apoptosis in hepatoma cells is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of mitochondrial pathway. Biochem Pharmacol701398-1407(2005).
Sesti, G., Cardellini, M., Marini, M.A., et al. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. Diabetes521280-1283(2003).
Zhang, C., Baffy, G., Perret, P., et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, b cell dysfunction, and type 2 diabetes. Cell105745-755(2001).