Chronic Administration of Dehydroepiandrosterone Reduces Pancreatic β-Cell Hyperplasia and Hyperinsulinemia in Genetically Obese Zucker Rats

The Zucker obese (fa/fa) rat is a model of hypertrophic/hyperplastic obesity. These rats develop marked hyperinsulinemia, insulin resistance, and pancreatic β-cell hyperplasia. In the present study, chronic (22 weeks) administration of the 17-ketosteroid, dehydroepiandrosterone (DHEA), to obese Zucker rats significantly decreased body weight, and retroperitoneal and parametrial fat pad weights. In addition, β-cell hyperplasia was reduced as well as pancreatic insulin content. DHEA treatment of lean Zucker rats also reduced body weight, fat depot weight, pancreatic islet diameter, and pancreatic insulin content. These data indicate that DHEA treatment appears to inhibit insulin synthesis and β-cell proliferation. Whether this is due to a direct effect on the pancreas or due to improvement of peripheral insulin sensitivity remains to be elucidated.