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Elevated D‐glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies
Author(s) -
Sobrevia L.,
Yudilevich D. L.,
Mann G. E.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.219bx.x
Subject(s) - medicine , endocrinology , umbilical vein , insulin , gestational diabetes , glucose transporter , arginine , prostacyclin , l glucose , diabetes mellitus , biology , chemistry , gestation , in vitro , biochemistry , islet , pregnancy , genetics , amino acid
1 The effects of human insulin and elevated D‐glucose on L‐arginine transport and synthesis of nitric oxide (NO) and prostacyclin (PGI 2 ) have been investigated in human umbilical vein endothelial cells isolated from gestational diabetic pregnancies. 2 The increase in the V max for L‐arginine transport (9.0 ± 1.1 pmol (μg protein) −1 min −1 ) in diabetic endothelial cells cultured in 5 mM D‐glucose was unaffected following 24 h exposure to 25 mM D‐glucose. 3 Gestational diabetes‐induced increases in basal intracellular cGMP and L‐citrulline levels (inhibitable by L‐NAME) and [Ca 2+ ] i were unaffected by elevated D‐glucose. In contrast, PGI 2 release was inhibited in diabetic cells exposed to either 5 or 25 mM D‐glucose. 4 Elevated D‐glucose attenuated histamine (10 μM, 5 min)‐stimulated accumulation of cGMP and L‐citrulline in endothelial cells isolated from gestational diabetic pregnancies. 5 The membrane hyperpolarization (‐79 ± 0.9 mV) sustained in diabetic endothelial cells in culture was insensitive to elevated D‐glucose. 6 Elevated D‐glucose abolished the stimulatory effect of human insulin (1 nM, 8 h) on L‐[ 3 H]leucine incorporation in diabetic endothelial cells cultured in 5 mM D‐glucose. 7 Human insulin reduced the elevated rates of L‐arginine transport and cGMP accumulation in diabetic cells cultured in 5 mM D‐glucose but failed to reduce increased rates of transport or NO production in cells exposed to 25 mM D‐glucose or cycloheximide. 8 Our findings demonstrate that hyperglycaemia impairs the actions of human insulin on umbilical vein endothelial cells isolated from gestational diabetic pregnancies. Changes in insulin sensitivity and/or its signalling cascade may be affected by hyperglycaemia associated with gestational diabetes, resulting in insulin resistance in endothelial cells derived from the fetal vasculature.