Human Endothelial Cells Are Defective in Diabetic Vascular Disease

Sank, A.; Wei, David; Reid, James J.; Ertl, Delia; Nimni, Marcel; Weaver, Fred A.; Yellin, Albert E.; Tuan, Tai‐Lan

doi:10.1006/jsre.1994.1195

Cited by 36 publications

(28 citation statements)

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“…An extensive literature supports the link between hyperglycemia and endothelial dysfunction (3,47,48,52); however, the contribution of changes in Ca 2ϩ homeostasis to endothelial dysfunction remains controversial (49,50). In the present study, exposing BAECs to HG for 4, 24, or 72 h had no effect on the amplitude of Ca 2ϩ released from the intracellular store but increased the sustained Ca 2ϩ entry phase following the activation of the P2Y receptor after 24 and 72 h in HG.…”

Section: Discussioncontrasting

confidence: 47%

Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

Bishara

Ding

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Hyperglycemia is a major risk factor for endothelial dysfunction and vascular disease, and in the current study, the link to glucose-induced abnormal intracellular Ca2+ (Cai2+) homeostasis was explored in bovine aortic endothelial cells in high glucose (HG; 25 mmol/l) versus low glucose (LG; 5.5 mmol/l; control). Transient receptor potential 1 (TRPC1) ion channel protein, but not TRPC3, TRPC4, or TRPC6 expression, was significantly increased in HG versus LG at 72 h. HG for 4, 24, and 72 h did not change basal Cai2+ or ATP-induced Cai2+ release; however, the amplitude of sustained Cai2+ was significantly increased at 24 and 72 h and reduced by low concentration of the putative, but nonspecific, TRPC blockers, gadolinium, SKF-96365, and 2-aminoethoxydiphenyl borate. Treatment with TRPC1 antisense significantly reduced TRPC1 protein expression and ATP-induced Ca2+ entry in bovine aortic endothelial cells. Although the link between HG-induced changes in TRPC1 expression, enhanced Ca2+ entry, and endothelial dysfunction require further study, the current data are suggestive that targeting these pathways may reduce the impact of HG on endothelial function.

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Section: Discussioncontrasting

confidence: 47%

Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

Bishara

Ding

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Umbilical vein endothelial cells isolated from women with IDDM exhibit changes in cellular activity such as increased plasma membrane fluidity, enhanced fluid phase endocytosis, and an increase in mitochondrial area, Weibel-Palade bodies and rough reticulum with wide cisternae (Cester et al 1996). Moreover, umbilical vein endothelial cells from women with IDDM are also less resistant to shear stress, take up ª_glucose more slowly and exhibit an increased expression of major basal membrane components (Sank et al 1994). These observations support our previous finding that 'diabetic-like' characteristics are maintained during prolonged culture of these cells in euglycaemic or hyperglycaemic media (Sobrevia, Jarvis & Yudilevich, 1994;Sobrevia et al 1995a site of a primary defect in IDDM and contribute to the development of vascular disease (Tooke, 1995;Sobrevia & Mann, 1997).…”

Section: Discussionmentioning

confidence: 99%

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

Sobrevía

Yudilevich

Mann

1998

The Journal of Physiology

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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. 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. 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. Elevated D‐glucose attenuated histamine (10 μM, 5 min)‐stimulated accumulation of cGMP and L‐citrulline in endothelial cells isolated from gestational diabetic pregnancies. The membrane hyperpolarization (‐79 ± 0.9 mV) sustained in diabetic endothelial cells in culture was insensitive to elevated D‐glucose. 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. 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. 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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“…The nature of the underlying processes is complex and not yet fully understood. Several lines of evidence suggest that vascular endothelial function is disturbed in diabetes (Fortes et al, 1983;Cagliero et al, 1991;Sank et al, 1991;Hein and King, 1996;Magill and Dananberg, 1996;Donnelly et al, 2000). In isolated mesenteric beds of Wistar rats with 6 months diabetes, a reduction in endothelium-dependent relaxation was found (Olbrich et al, 1996(Olbrich et al, , 1999.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Effect of a β₂-Adrenoceptor Stimulation on Hyperglycemia-Induced Endothelial Dysfunction

Kabat

Pönicke²,

Salameh³

et al. 2003

J Pharmacol Exp Ther

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To investigate whether ␤ 2 -adrenoceptors exist on endothelial cells and whether a ␤ 2 -adrenoceptor stimulation might prevent the development of hyperglycemia-induced endothelial dysfunction, porcine aortic endothelial cells (PAECs) were cultured and chronically exposed to either 5 mM D-glucose ("normoglycemia") or 20 mM D-glucose ("hyperglycemia"), with or without 100 nM salbutamol in absence or presence ofFor osmotic control, PAECs were exposed to 15 mM L-glucose. We measured nitric oxide release using the met-hemoglobin assay and assessed ␤-adrenoceptor density and subtypes by radioligand binding. Furthermore, we determined intracellular NADH and NADPH using high-performance liquid chromatography. High Dglucose concentrations but not L-glucose led to significantly reduced basal and stimulated nitric oxide release. Chronic salbutamol treatment significantly antagonized the impairment of the nitric oxide response, which was inhibited by ICI 118,551 but not by metoprolol. The number of giant cells was significantly increased in hyperglycemia, which could be prevented by salbutamol. Binding of the radioligand (Ϫ)-[ 125 I]iodocyanopindolol revealed a total ␤-adrenoceptor density of 29.8 Ϯ 3.7 (normoglycemic) and 30.3 Ϯ 3.6 (hyperglycemic) fmol/mg protein. Displacement by ICI 118,551 revealed ␤-adrenoceptor subtype distribution with 30.3 Ϯ 4.4 (normoglycemic) and 29.1 Ϯ 3.8% ␤ 2 -adrenoceptors. NADH production increased in hyperglycemia, which was completely prevented by salbutamol. We conclude that hyperglycemia in PAEC induces endothelial dysfunction with impaired nitric oxide release and that this can be prevented by ␤ 2 -adrenoceptor stimulation.An intriguing problem in antidiabetic therapy is the development of generalized angiopathy and concomitant hypertension in diabetes mellitus. The nature of the underlying processes is complex and not yet fully understood. Several lines of evidence suggest that vascular endothelial function is disturbed in diabetes (Fortes et al., 1983;Cagliero et al., 1991;Sank et al

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Human Endothelial Cells Are Defective in Diabetic Vascular Disease

Cited by 36 publications

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Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

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

Effect of a β₂-Adrenoceptor Stimulation on Hyperglycemia-Induced Endothelial Dysfunction

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Human Endothelial Cells Are Defective in Diabetic Vascular Disease

Cited by 36 publications

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Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

Glucose enhances expression of TRPC1 and calcium entry in endothelial cells

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

Effect of a β2-Adrenoceptor Stimulation on Hyperglycemia-Induced Endothelial Dysfunction

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Effect of a β₂-Adrenoceptor Stimulation on Hyperglycemia-Induced Endothelial Dysfunction