Animal experiment:

Twelve-week old male ob/ob mice are used in this study. A catheter is implanted into the right internal jugular vein before the hyperinsulinemic-euglycemic clamp. After recovery, mice are administered Eprotirome (0.3 mg/kg) via intraperitoneal injection for 10 days. On the day of the clamp experiment, conscious, overnight-fasted mice receive a primed (10 μCi) and constant rate intravenous infusion (0.1 μCi /min) of [3-3H] glucose to measure basal glucose turnover. After 60 to 75 minutes of labeled glucose infusion, the hyperinsulinemic-euglycemic clamp is performed with continuous infusion of insulin (12 mU/kg/min) and variable infusion of 25% glucose to maintain euglycemia (~120 mg/dL). Blood samples are collected by tail bleeding (approximately every 10 min) to measure blood glucose concentrations[1].

Eprotirome is a liver-selective thyroid hormone receptor agonist.

Eprotirome is a liver-selective thyroid hormone receptor agonist. Histological analysis of livers from mice treated with Eprotirome reveals that Eprotirome elicits a near complete elimination of lipid filled vacuoles that are characteristic of the livers from untreated control mice. Eprotirome treated mice also exhibit increased fasting glucose, but Eprotirome does not increase fasting insulin levels. Glucose levels of mice treated with Eprotirome continues to increase over time, leading to pronounced hyperglycemia by the end of the study. Temperature of mice treated with Eprotirome is decreased relative to untreated control mice[1].

[1]. Martagón AJ, et al. The amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice. PLoS One. 2015 Apr 7;10(4):e0122987.