Renal type i inositol 1,4,5-trisphosphate receptor is reduced in
streptozotocin-induced diabetic rats and mice.
Sharma, Kumar, Lewei Wang, Yanqing Zhu, Aurora Deguzman, Gao-Yuan Cao,
Richard B. Lynn and Suresh K. Joseph.
1Nephrology Division and 3Gastroenterology and Hepatology Division
of the Department of Medicine and 2Department of Anatomy, Pathology,
and Cell Biology, Thomas Jefferson University School of Medicine,
Philadelphia, Pennsylvania 19107
APStracts 5:0171F, 1998.
The mechanisms underlying glomerular hypertrophy and hyperfiltration
in diabetes remain unclear. We have previously demonstrated that the
cytokine transforming growth factor-b1 (TGF-b1) is increased in early
diabetic kidney disease and TGF-b1 inhibits the expression of the
inositol 1,4,5 trisphosphate (IP3) gated calcium channel, type I
IP3R, in mesangial cells. To test the hypothesis that reduced type I
IP3R may be important in diabetic kidney disease, we evaluated type I
IP3R expression in the kidney of streptozotocin-induced diabetic rats
and mice. Two-week old diabetic rats have decreased renal type I IP3R
protein and mRNA levels. Immunostaining of normal rat kidney
demonstrated presence of type I IP3R in glomerular and vascular
smooth muscle cells, whereas diabetic rats had reduced staining in
both compartments. Reduction of type I IP3R also occurred in parallel
with renal hypertrophy, increased creatinine clearance, and increased
renal TGF- [beta]1 expression in the diabetic rats. Two-week old
diabetic mice also had reduced renal type I IP3R protein and mRNA
expression in association with renal hypertrophy and increased TGF-b1
mRNA expression. These findings demonstrate that there is reduced
type I IP3R in glomerular and vascular smooth muscle cells in the
diabetic kidney, and may contribute to the altered renal
vasoregulation and renal hypertrophy of diabetes.
Received 19 November 1997; accepted in final form 17 September
1998.
APS Manuscript Number F362-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998