FGF21 transgenic (FGF21Tg) mice exhibit improved glycemic control and enhanced sensitivity to the hormones insulin and leptin. Under fed conditions, FGF21Tg mice have lower basal levels of leptin (Panel A), insulin (Panel B), and serum glucose (Panel C). When challenged with an overnight fast FGF21Tg mice are able to maintain appropriate glucose levels (Panel C) despite extremely low levels of insulin (Panel B). Additionally, FGF21Tg mice are capable of proper leptin regulation when fasted (Panel A). Blood samples from fed and 24-h fasted 12 wk old, male wild-type and FGF21Tg mice (n = 6 per group) were collected on ice before storage of plasma at –80°C. Insulin (Crystal Chem Inc., Downers Grove, IL), leptin (Crystal Chem Inc.) and total adiponectin (BioVendor Inc., Karasek, Czech Republic) were measured by specific ELISA. Glucose was measured using a Hitachi 912 clinical chemistry analyzer (Roche Diagnostics, Indianapolis, IN).