Binding, Internalization, and Degradation of Insulin in Vascular Endothelial Cells

Kaiser, Nurit; Vlodavsky, Israël; Tur-Sinai, A.; Fuks, Zvi; Cerasi, Erol

doi:10.2337/diacare.31.12.1077

Cited by 32 publications

(4 citation statements)

References 10 publications

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“…This finding, which is in accordance with previous studies [9,12], is in line with the concept of a saturable endothelial transport system for insulin delivery. A saturable transcapillary transport with the characteristics of a receptor‐mediated transpinocytotic process under physiological insulin concentrations has been described in vitro [21–23]. These findings were supported by the characterization of a vascular endothelial insulin receptor [24,25].…”

Section: Discussionmentioning

confidence: 85%

Transcapillary insulin transfer in human skeletal muscle

Herkner

Klein

Joukhadar

et al. 2003

Eur J Clin Investigation

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Section: Discussionmentioning

confidence: 85%

Transcapillary insulin transfer in human skeletal muscle

Herkner

Klein

Joukhadar

et al. 2003

Eur J Clin Investigation

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“…Insulin binding was studied using a modification of the methods of Kaiser et al [8]. The cells were plated into dishes with DMEM containing 0.5% FBS for 24 hours and incubated at 37℃ with Tris-Hepes binding buffer (50 mM Tris, 50 mM Hepes, 10 mM MgC1 2 , 2 mM EDTA, 10 mM dextrose, 10 mM CaC1 2 , 50 mM NaCl, 5 mM KCl, 0.5% crystalline BSA, pH 7.8) and [ 125 I]-insulin (0.5 µCi/well) for 0, 10, 20, 30, 60, and 90 minutes.…”

Section: Methodsmentioning

confidence: 99%

Angiotensin II Inhibits Insulin Binding to Endothelial Cells

Lee

et al. 2011

Diabetes Metab J

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BackgroundInsulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.MethodsAfter treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.ResultsAfter treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.ConclusionATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

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“…Early in vitro studies by King and Johnson [81] and others [90] suggested this was the case. However, in the canine hindlimb [85], the appearance of insulin in lymphatic drainage did not reach saturation point when plasma insulin was raised from high physiological to pharmacological concentrations.…”

Section: Movement Of Insulin Across the Endothelial Lining Of The Micmentioning

confidence: 99%

The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action

et al. 2009

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Evidence suggests that insulin delivery to skeletal muscle interstitium is the rate-limiting step in insulin-stimulated muscle glucose uptake and that this process is impaired by insulin resistance. In this review we examine the basis for the hypothesis that insulin acts on the vasculature at three discrete steps to enhance its own delivery to muscle: (1) relaxation of resistance vessels to increase total blood flow; (2) relaxation of pre-capillary arterioles to increase the microvascular exchange surface perfused within skeletal muscle (microvascular recruitment); and (3) the trans-endothelial transport (TET) of insulin. Insulin can relax resistance vessels and increase blood flow to skeletal muscle. However, there is controversy as to whether this occurs at physiological concentrations of, and exposure times to, insulin. The microvasculature is recruited more quickly and at lower insulin concentrations than are needed to increase total blood flow, a finding consistent with a physiological role for insulin in muscle insulin delivery. Microvascular recruitment is impaired by obesity, diabetes and nitric oxide synthase inhibitors. Insulin TET is a third potential site for regulating insulin delivery. This is underscored by the consistent finding that steady-state insulin concentrations in plasma are approximately twice those in muscle interstitium. Recent in vivo and in vitro findings suggest that insulin traverses the vascular endothelium via a trans-cellular, receptor-mediated pathway, and emerging data indicate that insulin acts on the endothelium to facilitate its own TET. Thus, muscle insulin delivery, which is rate-limiting for its metabolic action, is itself regulated by insulin at multiple steps. These findings highlight the need to further understand the role of the vascular actions of insulin in metabolic regulation.

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Binding, Internalization, and Degradation of Insulin in Vascular Endothelial Cells

Cited by 32 publications

References 10 publications

Transcapillary insulin transfer in human skeletal muscle

Transcapillary insulin transfer in human skeletal muscle

Angiotensin II Inhibits Insulin Binding to Endothelial Cells

The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action

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