Effect of glucose, pyruvate, and insulin on type 1 angiotensin II receptor expression in SV40-immortalized rabbit proximal tubule epithelial cells

Ambient glucose concentrations alter type 1 angiotensin II receptor (AT(1)R) expression in renal tissues. The direction of change in AT(1)R density may depend on the specific cell type and the capacity for that cell type to use glucose as an energy substrate. Given the effects of angiotensin II (Ang II) in proximal tubule epithelia, glucose-mediated fluctuations in AT(1)R expression could significantly after tubular Na+-H+ exchange and volume reabsorption. To determine if glucose influenced AT(1)R expression in cultured proximal tubule epithelial cells, SV40-immortalized rabbit proximal tubule epithelial cells (RPTEC) were exposed to 25 mmol (hi-glc) or 5 mmol glucose-containing serum-free medium (lo-glc) for seven to nine days, with or without an alternative energy substrate, pyruvate. AT(1)R expression, assessed by quantitative reverse-transcription polymerase chain reaction and specific I-125-Ang II binding, decreased in lo-glc medium (% reduction AT(1)R mRNA expression: 52 +/- 8%; N = 6; P < 0.005 vs. hi-glc; % reduction specific I-125-Ang II binding: 48 +/- 12%; N = 12; P < 0.03 vs. hi-glc). AT(1)R mRNA expression and specific I-125-Ang II binding recovered to hi-glc levels following the addition of pyruvate [60 mmol] to lo-glc cells. To ascertain if a growth factor that increases glucose uptake in vivo also altered AT(1)R expression, RPTEC were cultured in hi-glc medium with or without exogenous insulin [100 nM]. Insulin addition increased AT(1)R mRNA expression and specific I-125-Ang II binding in a concentration-dependent manner. However, insulin (100 nM) addition to lo-glc cells did not significantly increase specific I-125-Ang II binding. These results suggest that AT(1)R expression in SV40-immartalized rabbit proximal tubule cells is significantly affected by the availability of energy substrate. Ultimately, changes in proximal tubule AT(1)R expression, mediated by elevated glucose concentrations and insulin, could contribute to sodium-dependent hypertension in the setting of hyperinsulinemia and hyperglycemia.