Fig 4.

A chimeric FGF21 protein in which the FGF21 C-terminal tail had been swapped with that of FGF19 exhibits FGF21-like activity. (A) Immunoblot analysis of Egr1 expression in HEK293-βKlotho cells stimulated with FGF21 or FGF21^29–167/FGF19^169–216. Numbers above the lanes give the amounts of protein added in ng ml⁻¹. To control for equal sample loading, the protein blots were probed with an antibody to GAPDH. Note that the FGF21^29–167/FGF19^169–216 chimera is more potent than native FGF21 at inducing Egr1 expression, which is consistent with the SPR data shown in Fig. 2F. The data are representative of two independent experiments. (B) Analysis of blood glucose concentrations in mice before and at the indicated time points after intraperitoneal injection of insulin alone, insulin plus FGF21^29–167/FGF19^169–216, insulin plus FGF21, or vehicle alone. Insulin and FGF21 ligand were injected at 0.5 units per kg of body weight and 0.3 mg per kg of body weight, respectively. Blood glucose concentrations are expressed as percentages of preinjection values. Data are presented as means ± SEM. (C) Changes in plasma insulin concentrations in mice in response to a single intraperitoneal injection of FGF21^29–167/FGF19^169–216, FGF21, or vehicle. Three different doses of protein were tested, and the numbers below the x axis give each dose of protein injected in mg per kg of body weight. Plasma insulin concentrations are expressed as percentages of preinjection values. Data are presented as means ± SEM. *, P < 0.05; **, P < 0.01 (both by Student's t test).