title: Thyroid hormone ameliorates diabetic nephropathy in a mouse model of type II diabetes.
abstract: 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).
authors.affiliation: Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006943:Hyperglycemia / Q000517:prevention & control; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014284:Triiodothyronine / Q000008:administration & dosage*
chemical_list: C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014284:Triiodothyronine; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases