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Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability

Swärd, Per LU and Rippe, Bengt LU (2012) In Acta Physiologica 204(3). p.294-307
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... (More)
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 2030 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 60100 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
capillary permeability, diabetes, glomerular filtration, macromolecules, Rho-kinase
in
Acta Physiologica
volume
204
issue
3
pages
294 - 307
publisher
Wiley-Blackwell
external identifiers
  • wos:000299775100003
  • pmid:21812939
  • scopus:84856514036
ISSN
1748-1708
DOI
10.1111/j.1748-1716.2011.02343.x
language
English
LU publication?
yes
id
e783904a-6195-4a8d-84fb-fc0dca9812e6 (old id 2409791)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21812939?dopt=Abstract
date added to LUP
2012-04-02 09:32:07
date last changed
2017-09-24 03:11:14
@article{e783904a-6195-4a8d-84fb-fc0dca9812e6,
  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 2030 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 60100 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.},
  author       = {Swärd, Per and Rippe, Bengt},
  issn         = {1748-1708},
  keyword      = {capillary permeability,diabetes,glomerular filtration,macromolecules,Rho-kinase},
  language     = {eng},
  number       = {3},
  pages        = {294--307},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Acute and sustained actions of hyperglycaemia on endothelial and glomerular barrier permeability},
  url          = {http://dx.doi.org/10.1111/j.1748-1716.2011.02343.x},
  volume       = {204},
  year         = {2012},
}