Abstract：
Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia 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 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB 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 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U 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 glycemic 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.
摘要：
四氧嘧啶诱导的糖尿病大鼠出现甲状腺功能减退。当用三碘甲状腺原氨酸（T3）处理时，血糖和促炎细胞因子表达下调，提高胰岛素敏感性。在该实验模型中研究了T3与胰岛素[替代剂量（6U）和（3U）]在控制血糖方面的有效性。雄性Wistar大鼠通过四氧嘧啶注射制成糖尿病，并分为与T3（1.5µg100g-1BW）相关或不相关的胰岛素（3或6U）治疗或不治疗28天的组。对照组为非糖尿病大鼠。空腹血糖,在所有动物的血液/血清中测量葡萄糖衰减率和TSH。免疫印迹用于评估骨骼肌和附睾白色脂肪组织中的总GLUT4表达。在这些组织和肝脏中测量细胞因子和NF-kB表达。糖尿病大鼠呈现空腹血糖升高，炎症细胞因子和NF-kB表达，TSH水平和胰岛素抵抗。在用T3和/或胰岛素治疗的糖尿病大鼠中，这些参数减少了，而GLUT4和抗炎细胞因子表达增加。T3联合3U胰岛素使参数恢复到对照组的值，并且在控制血糖方面比6U胰岛素更有效。因此，T3和胰岛素的组合可能代表糖尿病管理的一个有希望的策略，因为它减少了一半的胰岛素需求和改善糖尿病大鼠的血糖控制。这可能会推迟长期胰岛素治疗导致的胰岛素抵抗。这些发现为使用提供组织特异性效应的甲状腺类似物开辟了一个视角，这可能会导致糖尿病的潜在更有效的治疗。
