Download PDF
Exp Clin Endocrinol Diabetes 1999; 107(5): 299-305
DOI: 10.1055/s-0029-1212116
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Increased glomerular cytosolic phospholipase A2 activity of OLETF rats with early diabetes

Y. Furuya1 , S. Tagami1 , A. Hasegawa1 , J. Ishii1 , J. Hirokawa1 , H. Yoshimura1 , T. Honda1 , S. Sakaue1 , K. Aoki1 , M. Murakami2 , I. Kudo2 , Y. Kawakami1
  • 1First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan
  • 2Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan
Further Information

Publication History

Publication Date:
14 July 2009 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A2 (cPLA2), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30—46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA2 activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA2 activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA2 activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.

Key words

Cytosolic phospholipase A2 - diabetic nephropathy - glomeruli - hyperfiltration - OLETF rats

      >