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Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.

Lubbad, Loay; Öberg, Carl M; Dhanasekaran, Subramanian; Nemmar, Abderrahim; Hammad, Fayez; Pathan, Javed Y; Rippe, Bengt LU and Bakoush, Omran LU (2015) In Physiological reports 3(5).
Abstract
Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular... (More)
Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20-90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50-69 Å = 0.001 vs. 0.0002, and θ for 70-90 Å = 0.0007 vs. 0.00006, P < 0.001), while θ for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (θ for 36-49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physiological reports
volume
3
issue
5
publisher
John Wiley & Sons
external identifiers
  • PMID:26009635
ISSN
2051-817X
DOI
10.14814/phy2.12397
language
English
LU publication?
yes
id
5108f777-4266-46d7-97a4-7a2f1a21a448 (old id 5442315)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26009635?dopt=Abstract
date added to LUP
2015-06-05 12:16:25
date last changed
2016-09-20 03:31:06
@misc{5108f777-4266-46d7-97a4-7a2f1a21a448,
  abstract     = {Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20-90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius &gt;50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50-69 Å = 0.001 vs. 0.0002, and θ for 70-90 Å = 0.0007 vs. 0.00006, P &lt; 0.001), while θ for FITC-Ficoll &lt;50 Å tended to be lower in diabetic rats than in controls (θ for 36-49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes.},
  author       = {Lubbad, Loay and Öberg, Carl M and Dhanasekaran, Subramanian and Nemmar, Abderrahim and Hammad, Fayez and Pathan, Javed Y and Rippe, Bengt and Bakoush, Omran},
  issn         = {2051-817X},
  language     = {eng},
  number       = {5},
  publisher    = {ARRAY(0x85abf88)},
  series       = {Physiological reports},
  title        = {Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.},
  url          = {http://dx.doi.org/10.14814/phy2.12397},
  volume       = {3},
  year         = {2015},
}