alexa Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Diabetes & Metabolism

Author(s): Swrd P, Rippe B

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Abstract Microalbuminuria is an established marker of systemic endothelial dysfunction, which for patients with diabetes signals an increased risk of both diabetic nephropathy and cardiovascular complications. A better understanding of the pathogenesis of microalbuminuria is important in the quest of finding new approaches to treat patients with diabetes. Direct acute effects of episodes of hyperglycaemia (HG) could have implications for the microalbuminuria seen in early diabetes before renal structural alterations have started, especially in those patients with poor glycaemic control. This review summarizes the literature evidence that acute or sustained HG may lead to an increased vascular or glomerular permeability. Special focus is on glomerular barrier permeability. There is evidence in the literature that HG increases systemic capillary and glomerular barrier permeability within 20-30 min in vivo in rats and mice. Furthermore, exposure of monolayers of cultured endothelial cells to HG has been shown to increase monolayer permeability rapidly and transiently (during 60-100 min). Instant cellular changes following F-actin cytoskeleton rearrangements, which could be abrogated by Rho-kinase (ROCK) inhibition, are implicated. Data in this review also suggest that activation of protein kinase C, the polyol pathway, and an increased release of reactive oxygen species (ROS) and cytokines could contribute to the increase in barrier permeability induced by HG. Recent in vitro data from cultured podocyte monolayers also designates a role of insulin in acute podocyte F-actin remodelling, underpinning the complexity of the mechanisms leading to glomerular and endothelial barrier alterations in diabetes mellitus. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society. This article was published in Acta Physiol (Oxf) and referenced in Journal of Diabetes & Metabolism

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