Type 2 diabetes is associated with an increased risk for developing fatty liver disease, which results in an increased incidence of diabetic nephropathy. Hence, the present study was conceived to identify transcriptional changes in the liver that can provide molecular mediators for increased risk of developing nephropathy associated with type 2 diabetes. Type 2 diabetes was rendered in male SD rats using both high-fat diet and low dose of streptozotocin (35 mg/kg, intraperitonially, i.p.). Hepatic gene expression profiling was performed in animals after development of diabetic nephropathy. The gene expression data were validated by RT-PCR, protein expression, and immunohistochemistry. Gene expression profiling data revealed dramatic increase in expression of PKC epsilon, TNF-alpha-induced protein (four- to seven-folds), and decrease in the expression of DGK eta in the liver of diabetic nephropathic rats. Furthermore, there was an increase in expression of genes regulating Rho signaling pathway, which was further confirmed by increase in Rho kinase activity. To the best of our knowledge, this is the first report which shows the involvement of PKC epsilon, DGK eta, Tnfaip, and Rho kinase in the liver of type 2 diabetic rats and its association with diabetic nephropathy.
© 2010 Wiley-Liss, Inc.