Aldosterone impairs insulin responsiveness in U-937 human promonocytic cells via the downregulation of its own receptor.
In an earlier study, we have reported an inhibition of insulin receptor (IR) mRNA levels and insulin binding by aldosterone in U-937 human promonocytic cells. In the present extension of our studies, we demonstrate that this inhibition by aldosterone had no effects on basal glucose transport or on basal thymidine incorporation into DNA, while the cell responsiveness reflected by the maximal response to insulin was decreased by 23% for glucose transport and by 31% for DNA synthesis after the aldosterone treatment. We also prove that this inhibition of the insulin response by aldosterone is mediated by a downregulation of the levels of mineralocorticoid receptors (MRs) (50% decrease) and their mRNA (50% decrease). In addition, the mineralocorticoid antagonist spironolactone reversed the decrease in MR mRNA levels elicited by aldosterone, which suggests the involvement of this receptor in the process.
Campión
J
J
Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University, Spain.
Maestro
B
B
Molero
S
S
Dávila
N
N
Carranza
M C
MC
Calle
C
C
D000450:Aldosterone / Q000494:pharmacology*; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D020298:U937 Cells
D007328:Insulin; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D012313:RNA; D011972:Receptor, Insulin; D005947:Glucose; D013936:Thymidine