analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes. Am J Physiol Endocrinol Metab 300: E287-E295, 2011. First published October 19, 2010 doi:10.1152/ajpendo.00308.2010 is the leading cause of end-stage renal disease. To date, the molecular mechanisms of DN remain largely unclear. The present study aimed to identify and characterize novel proteins involved in the development of DN by a proteomic approach. Proteomic analysis revealed that 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2), the key enzyme in ketogenesis, was increased fourfold in the kidneys of type 2 diabetic db/db mice. Consistently, the activity of HMGCS2 in kidneys and 24-h urinary excretion of the ketone body ␤-hydroxybutyrate (␤-HB) were significantly increased in db/db mice. Immunohistochemistry, immunofluorescence, and real-time PCR studies further demonstrated that HMGCS2 was highly expressed in renal glomeruli of db/db mice, with weak expression in the kidneys of control mice. Because filtered ketone bodies are mainly reabsorbed in the proximal tubules, we used RPTC cells, a rat proximal tubule cell line, to examine the effect of the increased level of ketone bodies. Treating cultured RPTC cells with 1 mM ␤-HB significantly induced transforming growth factor-␤1 expression, with a marked increase in collagen I expression. ␤-HB treatment also resulted in a marked increase in vimentin protein expression and a significant reduction in E-cadherin protein levels, suggesting an enhanced epithelial-to-mesenchymal transition in RPTCs. Collectively, these findings demonstrate that diabetic kidneys exhibit excess ketogenic activity resulting from increased HMGCS2 expression. Enhanced ketone body production in the diabetic kidney may represent a novel mechanism involved in the pathogenesis of DN.

A compact, repetitive pulsed power system has many applications, but some basic aspects of the breakdown characteristics need further investigation. The purpose of this paper is to investigate the breakdown characteristics of dry air with repetitive nanosecond pulses. The variables affecting the discharge conditions, including the applied pulse voltage, pulse repetition frequency, gap distance and gas pressure, are investigated. The relationship between the breakdown time lag, the repetitive stressing time, and the number of applied pulses to breakdown with pulse repetition rate, E-field strength and pressure are obtained, and the breakdown characteristics and mechanism are also discussed. It is suggested that activated neutral species and residual ions should be taken into account, and repetitive nanosecond-pulse breakdown is characterized by the accumulation effect.