Relationship between endothelial cell dysfunction and insulin signalling and resistance in pre-eclampsia

Ghosh, Anshuman (2018) Relationship between endothelial cell dysfunction and insulin signalling and resistance in pre-eclampsia. (MSc(R) thesis), Kingston University, .


Aim: The aim of the thesis was to investigate the hypothesis that (i) Changes in endothelial cell insulin signalling occur in pre-eclampsia, secondary to underlying endothelial dysfunction, resulting in insulin resistance, (ii) Impaired endothelial cell insulin signalling results in reduced tissue delivery of insulin and reduced GLUT-4 activation, and (iii) Impaired microvascular blood flow results in insulin resistance. Methods: Filtrass strain-gauge plethysmograph was used to measure human calf blood flow in women with pre-eclampsia and normotensive controls. Biochemical markers of endothelial dysfunction, ICAM-1, VCAM-1. TNF, eSelectin, Thrombomodulin, and cellular marker, CEC, provided information regarding endothelial dysfunction. Insulin resistance was calculated using HOMA. Cells were cultured in normotensive and pre-eclamptic serum to study the insulin signalling pathway, using flow cytometry and western Blot. Results: In this cross-sectional study, microvascular blood flow was reduced in the pre-eclamptic cohort, compared to normotensive controls. Insulin resistance was also increased in women with pre-eclampsia. Endothelial cell insulin receptor expression and Akt expression were reduced in the pre-eclamptic participants, compared to normotensive pregnant controls. However, there was no significant difference in total insulin receptor protein and Akt protein in between the two groups. There was also no difference in endothelial cell GLUT 4 expression in between the groups. Conclusion: Insulin Resistance in pre-eclampsia, correlates with endothelial dysfunction and microvascular blood flow. Although expression of insulin receptors and Akt in endothelial cells, are reduced in pre-eclampsia, this does not correlate with insulin resistance. Furthermore, as there is no change in endothelial cell GLUT4 expression, in between the two cohorts, it is unlikely to explain the Insulin Resistance seen in pre-eclampsia.

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