Panveloski-Costa Ana Carolina, Kuwabara Wilson Mitsuo Tatagiba, Munhoz Ana Cláudia, Lucena Camila Ferraz, Curi Rui, Carpinelli Angelo Rafael, Nunes Maria Tereza
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Interdisciplinar Health Science Post-Graduate Program, Cruzeiro do Sul University, São Paulo, Brazil.
Endocrine. 2020 May;68(2):287-295. doi: 10.1007/s12020-020-02208-5. Epub 2020 Jan 29.
Diabetes mellitus (DM) has a multifactorial etiology that imparts a particular challenge to effective pharmacotherapy. Thyroid hormone actions have demonstrated beneficial effects in diabetic as well as obese rats. In both conditions, inflammation status plays a crucial role in the development of insulin resistance. Taking this into consideration, the present study aimed to demonstrate another possible pathway of thyroid hormone action on insulin sensitivity in a spontaneous type 2 diabetic rat model: the Goto-Kakizaki (GK) rats. GK animals present all typical hallmarks of type 2 DM (T2DM), except the usual peripheric inflammatory condition, observed in the other T2DM animal models.
GK rats were treated or not with 3,5,3'triiodothyronine (T3). Insulin sensitivity, glucose tolerance, and proteins related to glucose uptake and utilization were evaluated in the skeletal muscle, white adipose tissue, and liver.
GK rats T3-treated presented enhanced insulin sensitivity, increased GLUT-4 content in the white adipose tissue and skeletal muscle, and increased hexokinase and citrate synthase content in skeletal muscle. Both non-treated and T3-treated GK rats did not present alterations in cytokine content in white adipose tissue, skeletal muscle, liver, and serum.
These results indicate that T3 improves insulin sensitivity in diabetic rats by a novel inflammatory-independent mechanism.
糖尿病（DM）具有多因素病因，这给有效的药物治疗带来了特殊挑战。甲状腺激素作用已在糖尿病大鼠和肥胖大鼠中显示出有益效果。在这两种情况下，炎症状态在胰岛素抵抗的发展中起着关键作用。考虑到这一点，本研究旨在证明在自发性2型糖尿病大鼠模型——Goto-Kakizaki（GK）大鼠中，甲状腺激素对胰岛素敏感性作用的另一种可能途径。GK动物呈现出2型糖尿病（T2DM）的所有典型特征，但在其他T2DM动物模型中观察到的外周炎症情况除外。
对GK大鼠给予或不给予3,5,3'-三碘甲状腺原氨酸（T3）治疗。评估骨骼肌、白色脂肪组织和肝脏中的胰岛素敏感性、葡萄糖耐量以及与葡萄糖摄取和利用相关的蛋白质。
接受T3治疗的GK大鼠胰岛素敏感性增强，白色脂肪组织和骨骼肌中GLUT-4含量增加，骨骼肌中己糖激酶和柠檬酸合酶含量增加。未治疗和T3治疗的GK大鼠在白色脂肪组织、骨骼肌、肝脏和血清中的细胞因子含量均未出现改变。
这些结果表明，T3通过一种新的非炎症机制改善糖尿病大鼠的胰岛素敏感性。
