Figure 2.

CLT-005 is effectively delivered systemically via oral gavage and is well tolerated by BN rats. (A) The baseline (4 days post STZ) and endpoint (16 weeks post STZ) weights were averaged for each group. Daily dosing of CLT-005 did not adversely affect weight gain at week 16 for any of the given doses when compared with the vehicle treatment. (B) Following 16 weeks of daily doses, whole blood was collected 3 hours after the terminal dose, and CLT-005 concentration in the plasma was measured by liquid chromatography/mass spectrometry (LC/MS). CLT-005 concentration in the plasma was dose dependent (mean ± SEM; *P < 0.05; **P < 0.01; Mann-Whitney nonparametric t-test). (C) Glucose levels were measured once a week for 16 weeks post STZ. All measurements within each group during the duration of the study were averaged and plotted (mean ± SEM). The groups receiving the two highest doses of CLT-005 had significantly lower average blood glucose levels during the course of the study when compared with the animals receiving either vehicle or 125 mg/kg CLT-005 (***P > 0.001; Mann-Whitney nonparametric t-test). (D) The baseline (4 days post STZ) and endpoint (16 weeks post STZ) nonfasting glucose levels were averaged for each group and plotted. The differences between baseline and endpoint glucose levels were greatest for the groups administered the two highest doses of CLT-005. (E) Retinas were dissected from animals within the indicated treatment group, and equal concentrations of protein were processed for SDS-PAGE, transferred to polyvinylidene fluoride (PVDF), and immunoblotted with the indicated antibodies. Stat3 activity is higher in the retinas of STZ-diabetic rats treated with vehicle or 125 mg/kg CLT-005 compared to the two highest doses of CLT-005.