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Diabetologia

, Volume 38, Issue 3, pp 298–305 | Cite as

Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan

  • P. Mahadevan
  • R. G. Larkins
  • J. R. E. Fraser
  • A. J. Fosang
  • M. E. Dunlop
Originals

Summary

Exposure in vivo or in vitro to elevated glucose increases production of vasoactive prostaglandins by glomeruli and mesangial cells. This study aimed to determine whether this increased prostaglandin production could provide a link with later structural changes in diabetic nephropathy. Glomerular cores were prepared from control rats and streptozotocin-diabetic rats (3 weeks' duration). Over 24 h in culture hyaluronan production from diabetic glomerular cores was higher than production from control glomerular cores whether maintained in 5.6 mmol/l glucose (105.6±15.5 vs 53.6±8.5 ng hyaluronan per 250 glomerular cores, p<0.001); in 25 mmol/l glucose (149.3±34.8 vs 62.7±7.8 ng hyaluronan per 250 glomerular cores, p<0.01); or in 45 mmol/l glucose (176.8±23.3 vs 102.0±17.9 ng hyaluronan per 250 glomerular cores, p<0.01). At 5.6 mmol/l glucose, exposure in vitro to prostaglandin E2 caused an increase in hyaluronan production [maximal at 10−9 mol/l prostaglandin E2, 237±19 vs 42±4, ng hyaluronan per 250 glomerular cores, p<0.001 (control) and 195±7 vs 103±5, ng hyaluronan per 250 glomerular cores, p<0.001 (diabetic)]. In both control and diabetic glomerular cores hyaluronan production was reduced significantly by the cyclooxygenase inhibitor indomethacin (10−5 mol/l) [24.7±3.33 vs 40.25±4.11 ng hyaluronan per 250 glomerular cores, p<0.05 (control) and 36.5±6.25 vs 118.0±22.6, p<0.01 (diabetic)]. A direct spectrophotometric microassay was used to determine the concentration of sulphated glycosaminoglycans derived from papain-digested glomerular core proteoglycans. Release of sulphated glycosaminoglycans from diabetic glomerular cores maintained at 5.6 mmol/l glucose was decreased [41.9±1.1 vs 54.0±1.0 Μg of sulphated glycosaminoglycans (chondroitin sulphate) per 250 glomerular cores p<0.01]. A decrease in sulphated glycosaminoglycans was also shown from control glomerular cores maintained at 25 mmol/l glucose. At this glucose concentration, addition of exogenous hyaluronan or prostaglandin E2 significantly reduced sulphated glycosaminoglycans from control and diabetic glomerular cores. It is concluded that increased prostaglandin production secondary to high glucose environment can lead to an increased glomerular hyaluronan synthesis. This can substantially affect the levels of sulphated glycosaminoglycans in the extracellular matrix. We propose that these effects provide a possible link between the initial biochemical consequences of hyperglycaemia and later structural changes seen in the glomerulus in diabetes.

Key words

Hyaluronan prostaglandin sulphated proteoglycan glycosaminoglycan mesangial cell 

Abbreviations

PG

Prostaglandins

GC

glomerular cores

STZ-D

streptozotocin diabetes

GAG

sulphated glycosaminoglycans

PDGF

platelet derived growth factor

PGE2

prostaglandin E2

STZ

streptozotocin

HSPG

heparan sulphate proteoglycan

HA

hyaluronan

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • P. Mahadevan
    • 1
  • R. G. Larkins
    • 1
  • J. R. E. Fraser
    • 1
  • A. J. Fosang
    • 1
  • M. E. Dunlop
    • 1
  1. 1.Department of Medicine, Royal Melbourne HospitalUniversity of MelbourneParkvilleAustralia

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