Aim: 

Recent evidences suggest that 3,5-diiodo-L-thyronine (T2) when administered to high fat diet (HFD) fed rats prevents adiposity. However, studies on T2 effects on insulin resistance are still lacking. In the present study we detected whether T2 administration to rats fed with an HFD can improve glucose tolerance.

Methods: 

3 groups of rats were used: rats receiving standard diet (N), rats receiving HFD (D), rats receiving HFD and a daily i.p. injection of T2 (25 mg/100 g b.w.) (DT). The experimental period lasted 4 weeks. Oral glucose tolerance test and measurement of insulin stimulated phosphorylation of protein kinase B (PKB/AKT) were performed. In liver mitochondria, oxidative stress and fatty acid oxidation rate were detected.

Results: 

D rats showed decreased glucose tolerance, while DT rats were characterized by improved glucose tolerance. In skeletal muscle, insulin-induced AKT phosphorylation was significantly decreased in D rats compared to N, whereas the administration of T2 to HFD fed rats increased AKT phosphorylation compared to D rats. At the hepatic level, T2 treatment increased mitochondrial fatty acid oxidation rate and decreased oxidative stress.

Conclusions: 

T2 treatment improves HFD-induced impaired glucose tolerance by both enhancing insulin-dependent AKT phosphorylation in skeletal muscle and improving hepatic metabolism.