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Am J Physiol. 1999 Jan;276(1):F54-61. doi: 10.1152/ajprenal.1999.276.1.F54.

Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice.

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Nephrology Division, Pathology, and Cell Biology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania 19107, USA.


The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-beta1 (TGF-beta1) is increased in early diabetic kidney disease and TGF-beta1 inhibits the expression of the inositol 1,4,5-trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (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-beta1 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-beta1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.

[Indexed for MEDLINE]

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