The leptin receptor has no role in delta-cell control of beta-cell function in the mouse

Leptin inhibits insulin secretion from isolated islets from multiple species, but the cell type that mediates this process remains elusive. Mouse models have been used to explore this question. Ablation of the leptin receptor (Lepr) throughout the pancreatic epithelium results in altered glucose homeostasis, ex vivo insulin secretion, and calcium dynamics. However, the removal of Lepr from neither alpha nor beta cells mimics these results. Because Lepr is enriched in the delta cells of human islets, we used a mouse model to test whether delta cells mediate the diminished glucose-stimulated insulin secretion in response to leptin. However, ablation of Lepr within mouse delta cells had no impact on glucose homeostasis or insulin secretion. We further demonstrate that Lepr is not appreciably expressed within mouse delta cells.