Journal Article

Glycaemic control with insulin prevents the reduced renal dopamine D<sub>1</sub> receptor expression and function in streptozotocin-induced diabetes

Mónica Moreira-Rodrigues, Janete Quelhas-Santos, Paula Serrão, Cátia Fernandes-Cerqueira, Benedita Sampaio-Maia and Manuel Pestana

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 9, pages 2945-2953
Published in print September 2010 | ISSN: 0931-0509
Published online March 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq150
Glycaemic control with insulin prevents the reduced renal dopamine D1 receptor expression and function in streptozotocin-induced diabetes

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Background. It was demonstrated in streptozotocin (STZ)-induced diabetic rats that the D1 receptor agonist failed to promote sodium excretion as a result of reduced renal D1 receptor expression and decreased receptor G protein coupling. The present study examined the influence of glycaemic control with insulin on the renal D1 receptor dysfunction in STZ-induced type 1 diabetes.

Methods. Renal function, blood pressure, the natriuretic response to 5% volume expansion (VE) and the effects of the D1 receptor agonist fenoldopam on natriuresis and on Na+/K+-ATPase activity in renal tubules were evaluated in uninephrectomized and sham-operated Wistar rats treated with STZ and compared with controls and STZ-treated rats made euglycaemic with insulin. D1 receptor immunohistochemistry and protein abundance by western blot were also determined in all groups.

Results. Treatment of sham and uninephrectomized rats with STZ caused a 4-fold increase in glucose plasma levels compared to controls and euglycaemic diabetic rats. A blunted natriuretic response to VE was observed in both sham and uninephrectomized hyperglycaemic diabetic rats, and this was accompanied by failure of fenoldopam to increase natriuresis and to inhibit renal Na+/K+-ATPase activity. In contrast, in both sham and uninephrectomized euglycaemic diabetic rats, the natriuretic response to VE, the fenoldopam-induced natriuresis and the accompanied inhibition of Na+/K+-ATPase activity were similar to those of the corresponding controls. D1 receptor immunodetection and protein abundance were reduced in hyperglycaemic diabetic rats, but not in euglycaemic diabetic animals.

Conclusions. We conclude that the renal expression and natriuretic response to D1 receptor activation is compromised in both sham and uninephrectomized rats with STZ-induced diabetes. These abnormalities were prevented by lowering glucose blood levels with insulin, thus providing evidence for the involvement of hyperglycaemia in the disturbances that underlie the compromised dopamine-sensitive natriuresis and increase of blood pressure in type 1 diabetes.

Keywords: blood pressure; dopamine; glycaemic control; natriuresis; streptozotocin and type 1 diabetes mellitus

Journal Article.  6137 words.  Illustrated.

Subjects: Nephrology

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