Therapeutical potential of T3 as adjuvant therapy in male alloxan-induced diabetic rats.

Alloxan-induced diabetic rats present hypothyroidism. When treated with triiodothyronine (T3), glycaemia and pro-inflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin [replacement dose (6U) and (3U)] in controlling glycaemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Non-diabetic rats constituted the control group. Fasting glycaemia, glucose decay rate and TSH were measured in the blood/sera of all animals. Immunoblotting was utilised to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and NF-kB expression were measured in these tissues and liver. Diabetic rats presented increased fasting glycaemia, inflammatory cytokines and NF-kB expression, TSH levels and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3U insulin restored the parameters to values of the control group and was more effective at controlling glycaemia than 6U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycaemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.