| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, Renal Research Group, Kolling Institute, University of Sydney, St. Leonards, Sydney, 2065, New South Wales, Australia
2 Department of Medicine, Renal Research Group, Kolling Institute, University of Sydney, St. Leonards, Sydney, 2065, New South Wales, Australia; School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, 4072, Queensland, Australia
3 Department of Endocrinology, Royal North Shore Hospital, St. Leonards, Sydney, 2065, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: carpol{at}med.usyd.edu.au.
Background: Post-prandial hyperglycaemia is implicated as a risk factor predisposing to vascular
complications. This study was designed to assess effects of recurrent short-term increases in glucose on markers of renal fibrogenesis.
Methods: Human renal cortical fibroblasts were exposed to fluctuating short-term (2 hour) increases to 15 mM D-glucose, 3 times a day over 72 hours, on a background of 5 mM D-glucose. To determine whether observed changes were due to fluctuating osmolality, identical experiments
were undertaken with cells exposed to L-glucose. Parallel experiments were performed in cells exposed to 5 mM D-glucose and constant exposure to either 15 mM or 7.5 mM D-glucose.
Results: Fluctuating D-glucose increased extracellular matrix, as measured by proline incorporation (P < 0.05), collagen IV (P < 0.005) and fibronectin production (P < 0.001), in association with increased tissue inhibitor of matrix metalloproteinase (P < 0.05). Sustained exposure to 15 mM D-glucose increased fibronectin (P < 0.001), in association with increased matrix metalloproteinase (MMP)-2 (P = 0.01) and MMP-9 activity (P < 0.05), suggestive of a protective effect on collagen matrix accumulation. Transforming growth factor 
1 (TGF1) mRNA was increased after short term (90 minute) exposure to 15 mM glucose (P < 0.05), and after 24 hour exposure to 7.5 mM (P < 0.05). Normalization of TGF1 secretion occurred within 48 hours of constant exposure to an elevated glucose. Fluctuating L-glucose also induced TGF1 mRNA and a pro-fibrotic profile, however to a lesser extent than observed with exposure to
fluctuating D-glucose.
Conclusions: The results suggest that exposure to fluctuating glucose concentrations increases renal interstitial fibrosis when compared to stable elevations in D-glucose. The effects are in part due to the inherent osmotic changes.
This article has been cited by other articles:
|
|
 |
|
  L. A. Maile, B. E. Capps, E. C. Miller, A. W. Aday, and D. R. Clemmons Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo Diabetes, October 1, 2008; 57(10): 2637 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ceriello, K. Esposito, L. Piconi, M. A. Ihnat, J. E. Thorpe, R. Testa, M. Boemi, and D. Giugliano Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients Diabetes, May 1, 2008; 57(5): 1349 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Mariappan, D. Feliers, S. Mummidi, G. G. Choudhury, and B. S. Kasinath High Glucose, High Insulin, and Their Combination Rapidly Induce Laminin-{beta}1 Synthesis by Regulation of mRNA Translation in Renal Epithelial Cells Diabetes, February 1, 2007; 56(2): 476 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zafiriou, S. R. Stanners, S. Saad, T. S. Polhill, P. Poronnik, and C. A. Pollock Pioglitazone Inhibits Cell Growth and Reduces Matrix Production in Human Kidney Fibroblasts J. Am. Soc. Nephrol., March 1, 2005; 16(3): 638 - 645. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
