Glucose regulates LXRα subcellular localization and function in rat pancreatic β-cells

Liver X receptors (LXRs) are members of the nuclear receptor superfamily, which have been implicated in lipid homeostasis and more recently in glucose metabolism. Here, we show that glucose does not change LXR alpha protein level, but affects its localization in pancreatic beta-cells. LXR alpha is found in the nucleus at 8 mM glucose and in the cytoplasm at 4.2 mM. Addition of glucose translocates LXRa from the cytoplasm into the nucleus. Moreover, after the activation of LXR by its synthetic non-steroidal agonist (T0901317), insulin secretion and glucose uptake are increased at 8 mM and decreased at 4.2 nM glucose in a dose-dependent manner. Furthermore, at low glucose condition, okadaic acid reversed LXR alpha effect on insulin secretion, suggesting the involvement of glucose signaling through a phosphorylation-dependent mechanism.