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Glycobiology Advance Access published online on October 9, 2003

Glycobiology, doi:10.1093/glycob/cwh011
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Submitted on August 12, 2003
Revised on September 17, 2003
Accepted on September 21, 2003

© 2003 Oxford University Press

ORIGINAL ARTICLES

Enhanced activity of serum and urinary hyaluronidases in streptozotocin-induced diabetic Wistar and GK rats

Mayumi Ikegami-Kawai 1, Ryouzo Okuda 1, Takashi Nemoto 1, Naoya Inada 1, and Tomoko Takahashi 1*

1 Institute of Medicinal Chemistry, Hoshi University, 2-4-41, Ebara, Shinagawaku, Tokyo 142-8501, Japan

* To whom correspondence should be addressed. E-mail: t-tomoko{at}hoshi.ac.jp.

Abstract

Using streptozotocin-induced diabetic Wistar and GK rats as models of type 1 and type 2 diabetes, respectively, we investigated the changes in serum and urinary hyaluronidase activity with the pathological progress. The serum hyaluronidase levels of streptozotocin-induced rats started to increase on the 3rd day after injection and thereafter maintained approx. 3-fold higher levels compared with control rats; those of GK rats were already higher (~2-fold) from the beginning of experiment. The increases of serum hyaluronidase activity in both diabetic rats were similar to those of blood glucose level, indicating that diabetes mellitus was accompanied by enhanced activity of circulating hyaluronidase from the early phase of its development. In zymography, every serum from diabetic and control rats gave two hyaluronidase isomers, a major 73-kDa band (Hyal-1 type) and a minor 132-kDa band, suggesting that the increases in serum hyaluronidase activity were not due to the appearance of novel isomers. The hyaluronidase activity in 24-h urine of streptozotocin-induced rats was 3-, 7-, and 11-fold higher at the 8th, 15th, and 18th week than that of control rats, respectively, while the urinary hyaluronidase activity of GK rats was not significantly different from controls. There was a good correlation between the urinary hyaluronidase activity and the albumin excretion. Thus the increase in urinary hyaluronidase activity may reflect enhanced glomerular permeability in streptozotocin-induced diabetic rats and may be a useful marker for diabetic nephropathy. Relative resistance to SDS-denaturation in zymography of rat serum and urinary hyaluronidases compared with human serum hyaluronidase are also shown.


diabetes, hyaluronidase, serum, urine, zymography
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