Elevated D‐glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies

Elevated D‐glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies
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D-葡萄糖升高会导致从妊娠糖尿病妊娠中分离出的人脐带内皮细胞胰岛素不敏感

DOI:
10.1111/j.1469-7793.1998.219bx.x
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发表时间:
1998
期刊:
The Journal of Physiology
影响因子:
--
通讯作者:
G. Mann
G. Mann
中科院分区:
--
文献类型:
--
作者:
L. Sobrevia;D. Yudilevich;G. Mann

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1在从妊娠糖尿病孕妇分离的人脐静脉内皮细胞中研究了人胰岛素和升高的D-葡萄糖对L-精氨酸转运和一氧化氮(NO)和前列环素(PGI 2)合成的影响。2在5 mM D-葡萄糖中培养的糖尿病内皮细胞中,暴露于25 mM D-葡萄糖24 h后,L-精氨酸转运的Vmax增加(9.0 ± 1.1 pmol(μg蛋白)−1 min−1)未受影响。3糖尿病引起的基础细胞内cGMP和L-瓜氨酸水平(可通过L-NAME恢复)和[Ca 2 +]i的增加不受D-葡萄糖升高的影响。相比之下,在暴露于5或25 mM D-葡萄糖的糖尿病细胞中,PGI 2释放受到抑制。4升高的D-葡萄糖减弱了组胺(10 μM,5 min)刺激的cGMP和L-瓜氨酸在妊娠糖尿病患者分离的内皮细胞中的蓄积。5培养的糖尿病内皮细胞中持续的膜超极化(-79 ± 0.9 mV)对升高的D-葡萄糖不敏感。6升高的D-葡萄糖消除了人胰岛素(1 nM,8 h)对在5 mM D-葡萄糖中培养的糖尿病内皮细胞中L-[3 H]亮氨酸掺入的刺激作用。7人胰岛素降低了在5 mM D-葡萄糖中培养的糖尿病细胞中L-精氨酸转运和cGMP积累的升高速率,但未能降低暴露于25 mM D-葡萄糖或放线菌酮的细胞中转运或NO产生的升高速率。8我们的研究结果表明,高血糖损害人胰岛素对从妊娠糖尿病孕妇分离的脐静脉内皮细胞的作用。胰岛素敏感性和/或其信号级联的变化可能受到妊娠糖尿病相关的高血糖症的影响,导致胎儿血管内皮细胞的胰岛素抵抗。
1 The effects of human insulin and elevated D‐glucose on L‐arginine transport and synthesis of nitric oxide (NO) and prostacyclin (PGI2) have been investigated in human umbilical vein endothelial cells isolated from gestational diabetic pregnancies. 2 The increase in the Vmax 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 [Ca2+]i were unaffected by elevated D‐glucose. In contrast, PGI2 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‐[3H]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.
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DOI: --
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