MECHANISM OF DIABETIC NEPHROPATHY: ROLE OF PROTEIN KINASE-C ACTIVATION —

Chronic hyperglycemia is the main cause of diabetic microvascular complications of the kidney and retina. Multiple theories have been proposed to explain the adverse effects of hyperglycemia, including increased flux through the polyol pathway, excessive formation of advanced glycation end-products, oxidative stress, and altered signaling pathways such as protein kinase C (PKC). This article will review the evidence that has been published in support of these theories for their role in causing the pathologies observed in the kidney and renal glomeruli of diabetic animals and humans. Special emphasis will be placed on the activation of the PKC pathway, a target with the potential of mediating the adverse effects of hyperglycemia and its resultant metabolites. At present, clinical trials are in progress to determine the efficacy of PKC-β isoform inhibitors for the treatment of diabetic microvascular complications. (Adv Stud Med. 2005;5(1A):S10-S19) DIABETIC NEPHROPATHY