Altered cellular calcium responsiveness to insulin in normal and hypertensive pregnancy


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Abstract

ObjectiveTo investigate the glucose-independent calcium-related effects of insulin in cells from subjects with normal and hypertensive pregnancies.MethodWe used Indo-I fluorescence spectroscopy to measure cytosolic free calcium levels (Cai) in peripheral blood mononuclear cells (PBM) from 17 women (aged 20-40 years), six nonpregnant controls (NPC), five pregnant normotensive (PNT) women and six pregnant hypertensive (PHT) women, before and 5, 30, 60,120 and 180min after in vitro incubation with 200 µU/ml insulin.ResultsBasal Cai levels were significantly higher in PHT women (175.2 ± 18.8 nmol/l) than they were in NPC women (122.8 ± 2.8 nmol/l) and PNT women (123.9 ± 3.5 nmol/l). The initial insulin-induced rise in Cai was similar in NPC (ΔCai 13.5 + 5.6 nmol/l) and PNT women (ΔCai 14.6 ± 3.7 nmol/l), but appeared blunted in PHT women (ΔCai 8.2 ± 3.5 nmol/l), and, for all pregnant subjects, was closely and inversely related to basal Cai Over time, in PNT women, ΔCai did not increase from the initial response (maximal ΔCai 20.5 ± 2.3 nmol/l) compared to NPC. The total cellular calcium response to insulin was also blunted in PNT women (the area under the calcium-response curve was 86 ± 3.4 versus 97.4 ± 6.5 nmol/l), but was excessive in PHT women (115.5 ± 6 nmol/l, P=0.05).ConclusionsHypertension in pregnancy is associated with excess Cai insulin raises Cai in PBM, and different alterations of ΔCai responsiveness to insulin occur both in normal and in hypertensive pregnancy. These cellular calcium alterations may help to explain altered tissue responsiveness to insulin and other hormones in pregnancy.

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