Hyperinsulinemia Precedes Insulin Resistance in Mice Lacking Pancreatic β-Cell Leptin Signaling

The adipocyte hormone leptin acts centrally and peripherally to regulate body weight and glucose homeostasis. The pancreatic β-cell has been shown to be a key peripheral target of leptin, with leptin suppressing insulin synthesis and secretion from β-cells both in vitro and in vivo. Mice with disrupted leptin signaling in β-cells (lepr flox/flox RIPcre tg+ mice) display hyperinsulinemia, insulin resistance, glucose intolerance, obesity, and …