title: Phospho-mTOR: a novel target in regulation of renal lipid metabolism abnormality of diabetes.
abstract: The activation of Akt has been proved to involve in the lipogenesis of diabetic nephropathy. However, it's still not clear whether mTOR, another main gene in PI3K/Akt pathway, is also involved in the renal lipogenesis of diabetes. In the present study, it was revealed that the phosphorylation of mTOR was up-regulated in the renal tubular cells of diabetic rats, followed by the over-expression of SREBP-1, ADRP and lipogenesis. Again, high glucose increased the expression of phospho-mTOR accompanied with SREBP-1 and ADRP up-regulation and lipid accumulation in HKC cells. Rapamycin, known as mTOR inhibitor, was used to inhibit the activation of mTOR, which prevented effectively high glucose-induced SREBP-1 up-regulation and lipogenesis in HKC cells. Furthermore, high glucose-stimulated HKC cells transfected with wild-type mTOR vector showed the enhanced SREBP-1 and lipid droplets, however, TE mTOR vector (kinase dead)-transfected HKC cells presented resistance to high glucose and decreased SREBP-1 expression and lipogenesis. These above data suggested that phospho-mTOR mediated lipid accumulation in renal tubular cells of diabetes and might be the potential targets for treating lipogenesis of diabetic nephropathy.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.forename: Lingling
authors.initials: L
authors.lastname: Xing
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Feng
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000070780:Perilipin-2; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602984:Plin2 protein, rat; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D020123:Sirolimus
keywords: Akt; Diabetic nephropathy; Lipogenesis; SREBP-1; mTOR