Tandem Inhibition of PKC in Diabetic Nephropathy

摘要

It is now more than 15 years since the initial reports of upregulation of protein kinase C (PKC) isoforms in the diabetic kidney and positive preclinical data with the PKC isoform inhibitor, ruboxistaurin. However, subsequent clinical studies with ruboxistaurin that failed to reach key primary end points and the failure of the PKC-α or PKC-β isoform knockout mice in the presence of diabetes to totally prevent the diabetes'-associated renal lesions have reduced the enthusiasm for targeting PKC isoforms in diabetic nephropathy. However, as reported in this issue of Diabetes, Menne et al. (1) have provided positive provocative data suggesting that dual inhibition of PKC-α and -[3 isoforms is a novel approach that warrants consideration in diabetic nephropathy. The work is strengthened by using not only a genetic approach, i.e., a double PKC isoform knockout mouse, but by also using a PKC-α/β inhibitor, albeit its specificity remains questionable.