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

Abstract：

:Ambient glucose concentrations alter type 1 angiotensin II receptor (AT1R) expression in renal tissues. The direction of change in AT1R 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 AT1R expression could significantly alter tubular Na(+)-H+ exchange and volume reabsorption. To determine if glucose influenced AT1R 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. AT1R expression, assessed by quantitative reverse-transcription polymerase chain reaction and specific 125I-Ang II binding, decreased in lo-glc medium (% reduction AT1R mRNA expression: 52 +/- 8%; N = 6; P < 0.005 vs. hi-glc; % reduction specific 125I-Ang II binding: 48 +/- 12%; N = 12; P < 0.03 vs. hi-glc). AT1R mRNA expression and specific 125I-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 AT1R expression, RPTEC were cultured in hi-glc medium with or without exogenous insulin [100 nM]. Insulin addition increased AT1R mRNA expression and specific 125I-Ang II binding in a concentration-dependent manner. However, insulin (100 nM) addition to lo-glc cells did not significantly increase specific 125I-Ang II binding. These results suggest that AT1R expression in SV40-immortalized rabbit proximal tubule cells is significantly affected by the availability of energy substrate. Ultimately, changes in proximal tubule AT1R expression, mediated by elevated glucose concentrations and insulin, could contribute to sodium-dependent hypertension in the setting of hyperinsulinemia and hyperglycemia.

journal_name

Kidney Int

journal_title

Kidney international

authors

Becker BN,Kondo S,Cheng HF,Harris RC

doi

10.1038/ki.1997.307

subject

Has Abstract

pub_date

1997-07-01 00:00:00

pages

87-92

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)60147-8

journal_volume

pub_type

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