Thyroid hormone ameliorates diabetic nephropathy in a mouse model of type II diabetes
Thyroid hormone ameliorates diabetic nephropathy in a mouse model of type II diabetes
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DOI：
10.1530/joe-10-0340
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发表时间：
2011-05-01
影响因子：
4
通讯作者：
Sun, Zhongjie
中科院分区：
文献类型：
--
作者：
Lin, Yi;Sun, Zhongjie
糖尿病患者的常规治疗，如严格的血糖控制，不能完全阻止糖尿病肾病的进展。II型糖尿病患者血清游离三碘甲状腺原氨酸（T-3）水平较低。本研究的目的是检验一个假设，即用T-3治疗将改善db/db小鼠（一种II型糖尿病模型）的糖尿病肾病。雄性db/db小鼠（16周）用T-3处理4周。测定尿白蛋白排泄量和血糖水平。收集肾脏进行组织学检查和转化生长因子-β 1（TGF-β 1）表达和磷脂酰肌醇3-激酶（PI 3 K）的分子测定。T-3减轻db/db小鼠的白蛋白尿，表明肾功能改善。在db/db小鼠中，T-3显著降低皮质结缔组织中胶原成分的积累（间质纤维化）和肾小球中系膜基质的扩张（肾小球硬化），并防止肾小球丢失。因此，T-3改善了糖尿病小鼠的肾脏结构损伤。值得注意的是，糖尿病肾病伴随着肾脏中PI 3 K活性的显著降低和TGF-β 1表达的增加。在db/db小鼠中，T-3恢复肾脏PI 3 K活性，减轻高血糖，并降低肾脏TGF-β 1表达。同时给予PI 3 K抑制剂LY 294002可阻断T-3的上述作用。这些数据表明，T-3通过改善胰岛素信号传导（例如，G. PI 3 K活性）。内分泌学杂志（2011）209，185-191
Conventional therapies for diabetic patients, such as strict glycemic control, do not completely stop the progression of diabetic nephropathy. Serum-free tri-iodothyronine (T-3) levels were lower in patients with type II diabetes. The purpose of this study was to test a hypothesis that treatment with T-3 would improve diabetic nephropathy in db/db mice, a model of type II diabetes. Male db/db mice (16 weeks) were treated with T-3 for 4 weeks. Urinary excretions of albumin and blood glucose levels were measured. Kidneys were collected for histological examination and molecular assays of transforming growth factor-beta 1 (TGF-beta 1) expression and phosphatidylinositol 3-kinase (PI3K). T-3 attenuated albuminuria in db/db mice, suggesting an improved kidney function. T-3 significantly decreased accumulation of collagenous components in cortical interstitium (interstitial fibrosis) and expansion of mesangial matrix in glomeruli (glomerulosclerosis) and prevented the loss of glomeruli in db/db mice. Therefore, T-3 improved the renal structural damage seen in diabetic mice. Notably, diabetic nephropathy was accompanied by a significant decrease in PI3K activity and an increase in TGF-beta 1 expression in kidneys. T-3 restored renal PI3K activity, attenuated hyperglycemia, and decreased renal TGF-beta 1 expression in db/db mice. These effects of T-3 were abolished by simultaneous treatment with PI3K inhibitor (LY294002). These data suggest that T-3 prevented progressive kidney damage and remodeling in db/db mice by improving insulin signaling (e. g. PI3K activity). Journal of Endocrinology (2011) 209, 185-191