It has been shown that glomerular angiotensin II (ANG II) receptors are downregulated and protein kinase C (PKC) is activated under diabetic conditions. We, therefore, investigated ANG II receptor and PKC isoform regulation in glomerular mesangial cells (MCs) under normal and elevated glucose concentrations. MCs were isolated from collagenase-treated rat glomeruli and cultured in medium containing normal or high glucose concentrations (5.5 and 25.0 mM, respectively). Competitive binding experiments were performed using the ANG II antagonists losartan and PD-123319, and PKC analysis was conducted by Western blotting. Competitive binding studies showed that the AT₁ receptor was the only ANG II receptor detected on MCs grown to either subconfluence or confluence under either glucose concentration. AT₁ receptor density was significantly downregulated in cells grown to confluence in high-glucose medium. Furthermore, elevated glucose concentration enhanced the presence of all MC PKC isoforms. In addition, PKC, PKC and PKC were translocated only in cells cultured in elevated glucose concentrations following 1-min stimulation by ANG II, whereas PKC, PKC, and PKC were translocated by ANG II only in cells grown in normal glucose. Moreover, no changes in the translocation of PKC, PKC, PKC, and PKCµ were detected in response to ANG II stimulation under euglycemic conditions. We conclude that MCs grown in high glucose concentration show altered ANG II receptor regulation as well as PKC isoform translocation compared with cells grown in normal glucose concentration.

angiotensin II receptor; protein kinase C; mesangial cell; glucose

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