Glucose modifies the cross‐talk between insulin and the β‐adrenergic signalling system in vascular smooth muscle cells
作者:
Jun-ichi Kawabe,
Yoshiaki Aizawa,
Naohumi Takehara,
Naoyuki Hasebe,
Kenjiro Kikuchi,
期刊:
Journal of Hypertension
(OVID Available online 2000)
卷期:
Volume 18,
issue 10
页码: 1457-1464
ISSN:0263-6352
年代: 2000
出版商: OVID
关键词: insulin;glucose;adrenaline;mitogen-activated protein kinase;phosphoinositide 3-kinase;vascular smooth muscle cells
数据来源: OVID
摘要:
BackgroundAbnormalities in the vascular function of insulin are observed in insulin resistance, and hyperglycaemia is one of the important factors inducing insulin resistance.ObjectiveTo investigate the role of glucose in the interaction of insulin and β-adrenergic signalling systems in vascular smooth muscle cells (VSMC).MethodsAfter cells were treated with D-glucose (5– 25 mmol/l) and insulin (100 nmol/l), adenylyl cyclase activity was measured in the presence of isoproterenol, forskolin, and cholera toxin. Assays for insulin-induced activities of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) were performed.ResultsIn the presence of low glucose concentrations (5 mmol/l), insulin enhanced isoproterenol-, forskolin-and cholera toxin-stimulated adenylyl cyclase activities. This stimulatory effect was abolished by PI3-K inhibitors, wortmannin, or LY294002. In contrast, in the presence of high glucose concentrations (25 mmol/l), insulin attenuated isoproterenol-stimulated activity but not cholera toxin-or forskolin-stimulated activity. Insulin-stimulated activities of IRS-1 and PI3-K, but not MAPK activity, were also attenuated in the presence of high concentrations of glucose. The MAPK kinase inhibitor, PD98059, abolished the inhibitory effect of insulin on the β-adrenergic signalling system. Troglitazone and pioglitazone prevented this inhibitory effect of insulin by restoring IRS-1 and PI3-K activities.ConclusionsIn the presence of low glucose concentrations, insulin stimulates the β-adrenergic signalling system through the IRS-1/PI3-K pathway. However, in the presence of high glucose concentrations, the effect of insulin is switched to an inhibitory one, through the MAPK pathway. Our finding suggests that high glucose concentrations modify the cross-talk between insulin and the β-adrenergic signalling systems in VSMC.
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