Bratislava Medical Journal Vol.116, No.1, p.57-63, 2015

Objectives: The aim of study was to determine the renal effects of glucose transporter 4 (GLUT4) in a hypertensive nephropathy rat model.
Background: GLUT4 has been implicated in insulin resistance and hypertension in several animal models; however its role in hypertensive nephropathy still remains unclear.
Methods: Hypertensive nephropathy was induced by Nω-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, 100 mg/ml in drinking water and high salt (HS) diet (4 % NaCl), for 15 days in the presence of insulin, a GLUT 4 agonist (1 U/day) and indinavir, a GLUT4 inhibitor (80 mg/kg/day).
Results:

Decreased basal renal medullary and cortical blood flow was enhanced in LNNA/HS/indinavir group (p < 0.01) but attenuated (p < 0.05) by insulin.

Proteinuria was increased (p < 0.01) in LNNA/HS/indinavir group but attenuated (p < 0.01) by insulin.

Insulin-treated rats decreased urine NO (p < 0.01) and urine Na2+ (p < 0.01) compared to other treated animals.

In indinavir-treated animals, urine Na2+ was increased by benzamil, an epithelial sodium channel (ENaC) inhibitor (p < 0.01) and hydrochlorothiazide, a sodium/chloride co-transporter (NCC) inhibitor (p < 0.05).

Conclusion: GLUT4 exerts a renoprotective role which may be related to increase NO production. The antinatriuretic effects of GLUT4 appear to be due to enhancement of ion transport activity of ENaC and NCC at the renal tubules (Fig. 9, Ref. 34).