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

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Mónica Moreira-Rodrigues (Author) ICBAS; Quelhas Santos, J (Author) Other; Paula Serrão (Author) Other; Cátia Fernandes-Cerqueira (Author) Other; Benedita Sampaio-Maia (Author) FMDUP; Pestana M (Author) FMUP

Journal

Title: Nephrology Dialysis Transplantation

Vol. 25 No. 9

Pages: 2945-2953

ISSN: 0931-0509

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 16 Citations

ISI Web of Science

Scopus - 18 Citations

Pubmed / Medline

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Health sciences > Medical sciences > Medicine

Other information

Authenticus ID: P-003-3QD

DOI: 10.1093/ndt/gfq150

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

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9