Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
J Endocrinol. 2011 May;209(2):185-91. doi: 10.1530/JOE-10-0340. Epub 2011 Feb 9.
Conventional therapies for diabetic patients, such as strict glycemic control, do not completely stop the progression of diabetic nephropathy. Serum-free tri-iodothyronine (T₃) levels were lower in patients with type II diabetes. The purpose of this study was to test a hypothesis that treatment with T₃ would improve diabetic nephropathy in db/db mice, a model of type II diabetes. Male db/db mice (16 weeks) were treated with T₃ 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-β1 (TGF-β1) expression and phosphatidylinositol 3-kinase (PI3K). T₃ attenuated albuminuria in db/db mice, suggesting an improved kidney function. T₃ 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, T₃ 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-β1 expression in kidneys. T₃ restored renal PI3K activity, attenuated hyperglycemia, and decreased renal TGF-β1 expression in db/db mice. These effects of T₃ were abolished by simultaneous treatment with PI3K inhibitor (LY294002). These data suggest that T₃ prevented progressive kidney damage and remodeling in db/db mice by improving insulin signaling (e.g. PI3K activity).
传统的糖尿病患者治疗方法，如严格控制血糖，并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（T₃）水平较低。本研究旨在验证一个假设，即 T₃治疗可改善 db/db 小鼠（Ⅱ型糖尿病模型）的糖尿病肾病。16 周龄雄性 db/db 小鼠用 T₃治疗 4 周。测量尿白蛋白排泄和血糖水平。收集肾脏进行组织学检查和转化生长因子-β1（TGF-β1）表达和磷脂酰肌醇 3-激酶（PI3K）的分子分析。T₃可减轻 db/db 小鼠的白蛋白尿，提示肾功能改善。T₃可显著减少皮质间质胶原成分的堆积（间质纤维化）和肾小球系膜基质的扩张（肾小球硬化），并防止 db/db 小鼠肾小球丢失。因此，T₃改善了糖尿病小鼠的肾脏结构损伤。值得注意的是，糖尿病肾病伴有肾脏 PI3K 活性显著降低和 TGF-β1 表达增加。T₃可恢复 db/db 小鼠肾脏的 PI3K 活性，减轻高血糖，并降低肾脏 TGF-β1 表达。同时用 PI3K 抑制剂（LY294002）治疗可消除 T₃的这些作用。这些数据表明，T₃通过改善胰岛素信号（如 PI3K 活性）预防 db/db 小鼠进行性肾脏损伤和重塑。
