Derived from adrenal cortical, dehydroepiandrosterone-sulfate (DHEAS) is a precursor to androgens and estrogens, with various bioactivities. Although it has the property of anti-diabetes, the long-term effect of DHEAS on insulin secretion in beta-cells is still unclear. In this study, the effect of DHEAS on the insulin secretion activity in MIN6 cell lines in vitro was assessed. Insulin biosynthesis and secretion were stimulated by DHEAS for 24 h. DHEAS inhibited the AMPK activation and upregulated the expression of ACC-1. These findings indicate that DHEAS may exert prominent stimulatory effects on insulin secretion partly via AMPK inhibition and ACC-1 upregulation. (C) 2013 Elsevier Inc. All rights reserved.