LAUSR

Diabetes increases the risk of renal ischemia/reperfusion injury (IRI). Recent evidence suggests that tubular dysfunction is associated with glomerular impairment, but its causal relationship is unclear. Renal tubules have abundant mitochondria; Akt is translocated into mitochondria upon IRI. To test the hypothesis that tubular mitochondrial Akt1 (mito-Akt) plays a protective role during IRI and subsequent renal failure, we have generated novel renal tubule-specific transgenic mice harboring inducible mitochondria-targeting dominant negative Akt1 (KMDAKT) or constitutively active Akt1 (KMCAKT) with the Cre-lox system. After KMDAKT mice were induced with tamoxifen (T) and subjected to IRI, histological analysis showed increased tubule injury index Jablonski score (p Summary: 1] tubular mito-Aktcritically modulated the outcomes of kidney IRI beyond renal tubules, 2] tubular mitochondria dysfunction causally triggered development of glomerulosclerosis during acute and chronic kidney failure, and 3] renal tubular mito-Akt, which is activated by insulin, may represent a novel therapeutic target for diabetic nephropathy. Disclosure H.Y. Lin: None. Y. Chen: None. A. Ta: None. H. Lee: None. Y. Chen: None. P.H. Wang: None.