Altered cellular calcium responsiveness to insulin in normal and hypertensive pregnancy

Objective To investigate the glucose-independent calcium-related effects of insulin in cells from subjects with normal and hypertensive pregnancies. Method We used Indo-I fluorescence spectroscopy to measure cytosolic free calcium levels (Ca,) 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 180 min after in vitro incubation with 200 mu U/ml insulin. Results Basal Ca-i 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 Ca-i was similar in NPC (Delta Ca-i 13.5 +/- 5.6 nmol/l) and PNT women (Delta Ca-i 14.6 +/- 3.7 nmol/l), but appeared blunted in PHT women (Delta Ca-i 8.2 +/- 3.5 nmol/l), and, for all pregnant subjects, was closely and inversely related to basal Ca-i. Over time, in PNT women, Delta Ca-i did not increase from the initial response (maximal Delta Ca-i 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). Conclusions Hypertension in pregnancy is associated with excess Ca-i insulin raises Ca-i in PBM, and different alterations of Ca-i 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.