Role for Poly(ADP-ribose) Polymerase Activation in Diabetic Nephropathy, Neuropathy and Retinopathy

Authors: Obrosova, Irina G.; Julius, Ulrich A.

Source: Current Vascular Pharmacology, Volume 3, Number 3, July 2005 , pp. 267-283(17)

Publisher: Bentham Science Publishers

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Abstract:

Chronic complications of diabetes mellitus e.a. diabetic nephropathy, neuropathy and retinopathy develop in at least 30-50% of patients with both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes, and are the major cause of increased morbidity and mortality. The ultimate consequences of diabetes complications include renal failure, foot ulceration and amputation, and blindness. The magnitude of the problem and its economic impact make extremely important to understand the natural history of chronic diabetes complications and to identify more successful preventive and therapeutic options. The pathogenesis of diabetes complications involves multiple mechanisms. The importance of vascular component is well recognized in diabetic retinopathy, which is primarily a vascular disease, as well as diabetic nephropathy developing as a result of complex interplay between hemodynamic and metabolic factors. The importance of vascular versus non-vascular mechanisms in the pathogenesis of diabetic neuropathy remains a subject of debate. Studies in animal and cell culture models revealed that such mechanisms as increased aldose reductase activity, nonenzymatic glycation/glycoxidation, activation of protein kinase C, impaired growth factor support, enhanced oxidative/ nitrosative stress, and its downstream effectors such as mitogen-activated protein kinase activation, inflammatory response, endothelin-1 overexpression and impaired Ca++ signaling, play an important role in all three tissue-targets for diabetes complications i.e. kidney, retina and peripheral nerve. Evidence for important role of the downstream effector of free radical and oxidant-induced DNA injury, poly(ADP-ribose) polymerase activation, is emerging. This review describes recent studies addressing the role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy.

Keywords: type diabetes; hyperglycemia; glycoxidation; protein kinase c; glomerular injury; lipooxygenase; signal transduction

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570161054368634

Affiliations: 1: Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA.

Publication date: 2005-07-01

More about this publication?

Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.

Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.

Debates will also be encouraged in the correspondence section of this journal.

Role for Poly(ADP-ribose) Polymerase Activation in Diabetic Nephropathy, Neuropathy and Retinopathy

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