Dehydroepiandrosterone Sulfate and -Cell Function Enhanced Glucose-Induced Insulin Secretion and Altered Gene Expression in Rodent Pancreatic -Cells

Administration of dehydroepiandrosterone (DHEA), or its sulfated form (DHEAS), controls hyperglycemia in diabetic rodents without directly altering insulin sensitivity. We show that DHEAS enhanced glucose-stimulated insulin secretion when administered in vivo to rats or in vitro to -cell lines, without changing cellular insulin content. Insulin secretion increased from 3 days of steroid exposure in vitro, suggesting that DHEAS did not directly activate the secretory processes. DHEAS selectively increased the -cell mRNA expression of acyl CoA synthetase-2 and peroxisomal acyl CoA oxidase in a time-dependent manner. Although DHEAS is a peroxisomal proliferator, it did not alter the mRNA expression of peroxisomal proliferator–activated receptor (PPAR) or , or enhance the activity of transfected PPAR , , or in vitro. Thus, DHEAS directly affected the -cell to enhance glucose-stimulated insulin secretion and increased the mRNA expression of specific -cell mitochondrial and peroxisomal lipid metabolic enzymes. This effect of DHEAS on insulin secretion may contribute to the amelioration of hyperglycemia seen in various rodent models of diabetes. Diabetes 49:2012–2020, 2000