ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and beta-cell function. Elovl6 is expressed in both islets and beta-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and beta-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6-/- islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per beta-cell and diabetes. (C) 2014 Elsevier Inc. All rights reserved.