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The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy
Author(s) -
Curtis T. M.,
Scholfield C. N.
Publication year - 2004
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.431
Subject(s) - diabetic retinopathy , diabetes mellitus , medicine , pathogenesis , protein kinase c , population , downregulation and upregulation , retinopathy , oxidative stress , endocrinology , kinase , biology , microbiology and biotechnology , biochemistry , environmental health , gene
Diabetic retinopathy is one of the most common complications of diabetes and is a major cause of new blindness in the working‐age population of developed countries. While the exact pathogenic basis of this condition remains ill defined, it is clear that hyperglycaemia is a critical factor in its aetiology. Protein kinase C (PKC) activation is one of the sequelae of hyperglycaemia and it is thought to play an important role in the development of diabetic complications. This review questions the currently held dogma that PKC stimulation in diabetes is solely mediated through the overproduction of palmitate and oleate enriched diacylglycerols. Blood glucose concentrations are closely tracked by changes in the levels of free fatty acids and these, in addition to oxidative stress, may account for the aberrant activation of PKCs in diabetes. Little is known about why PKCs fail to downregulate in diabetes and efforts should be directed towards acquiring such information. Considerable evidence implicates the PKCβ isoform in the pathogenesis of diabetic retinopathy, but other isoforms may also be of relevance. In addition to PKCs, it is evident that novel diacyglycerol‐activated non‐kinase receptors could also play a role in the development of diabetic complications. Therapeutic agents have been developed to inhibit specific PKC isoforms and PKCβ antagonists are currently undergoing clinical trials to test their toxicity and efficacy in suppressing diabetic complications. The likely impact of these drugs in the treatment of diabetic patients is considered. Copyright © 2004 John Wiley & Sons, Ltd.