Alfuzosin ameliorates diabetes by boosting PGK1 activity in diabetic mice.

AIMS:Diabetes mellitus (DM) has become a global problem, causing a huge economic burden. The purpose of this study is to find a new potential method and mechanism for the treatment of DM. MAIN METHODS:The oxidation, glycation and insulin resistance cell models were built to screen the potential anti-diabetic chemicals. Then the DM mice were induced by the combination of high-fat diet (HFD) and intraperitoneal injection of streptozotocin (50 mg/kg) for five days. The alfuzosin (1.2 mg/kg) was administered by intraperitoneal injection once daily for sequential 12 weeks. Fasting blood glucose, blood lipid, oxidative stress and key markers of glucose metabolism were detected. PGK1/AKT/GLUT4 pathway related proteins were analyzed by Western blot. KEY FINDINGS:Alfuzosin ameliorated oxidative stress, glycative stress and insulin resistance in HepG2 cells. Further, in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, alfuzosin reduced fasting blood glucose, improved insulin sensitivity. Mechanically, alfuzosin activated PGK1 directly to stimulate the protein kinase B (AKT) signaling pathway, thus facilitating glucose uptake as well as improving insulin resistance. SIGNIFICANCE:The present finding has shed a new light on the treatment of DM and provides validation for PGK1 as a therapeutic target for DM.