Angiotensin II Inhibits Insulin Binding to Endothelial Cells

Oh, Seungbae; Ha, Won-Chul; Lee, Jee-In; Sohn, Tae Seo; Kim, Jihyun; Lee, Jungmin; Chang, Sang-Ah; Hong, Oak‐Kee; Son, Hyun-Shik

doi:10.4093/dmj.2011.35.3.243

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…Ang II increases blood flow, but appears to impair insulin-mediated glucose metabolism, without altering the access of insulin to the muscle interstitium [89]. These data on insulin access are not consistent with other published data, indicating that Ang II can reduce the number of insulin receptors on endothelial cells, which may lead to a reduction in receptor-mediated transcytosis [90], if insulin transport is indeed receptor-mediated. Some of these inconsistences may be due to the time of exposure to the vasoconstrictor: one study has shown that short-term Ang II can increase NO production, but long-term can reduce NO bioavailability [91].…”

Section: Factors That Can Induce Capillary Recruitmentcontrasting

confidence: 64%

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Kolka¹

2016

Microcirculation Revisited - From Molecules to Clinical Practice

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Skeletal muscle is a major metabolic organ that plays a critical role in regulating glucose homeostasis and lipid utilization. Impaired muscle metabolic response is evident in diseases such as diabetes, obesity and cardiovascular diseases, and is also often associated with microvascular dysfunction. Here, we investigate the changes that can occur in the muscle microvasculature and the profound impact they can have on metabolism. Under basal conditions, vasoactive compounds are able to affect metabolism in muscle by providing more glucose and oxygen to resting muscle. Insulin and exercise increase the perfusion of muscle, and thus provide more microvascular surface area, increasing the delivery of these metabolites to muscle. Endothelial dysfunction can therefore impair the delivery of oxygen, glucose and hormones to muscle, both through effects on blood flow distribution and the transport of these factors across the endothelium, leading to a decrease in oxygen consumption and glucose metabolism. Obesity and diabetes are associated with endothelial dysfunction and are accompanied by underlying changes in metabolism and reductions in insulin sensitivity. The muscle is a highly metabolic organ, and the vasculature is essential to maintain appropriate metabolic response; therefore, the muscle microcirculation may be a target for treating metabolic disease.

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Section: Factors That Can Induce Capillary Recruitmentcontrasting

confidence: 64%

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Kolka¹

2016

Microcirculation Revisited - From Molecules to Clinical Practice

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“…Each of these actions of Ang II can independently impair the vasodilatory actions of insulin in the microvasculature. In addition to these deleterious actions, Ang II directly impairs insulin signaling pathways in the endothelium (Kim, Jang, Martinez-Lemus et al, 2012, Maeno, Li, Park et al, 2012, Andreozzi, Laratta, Sciacqua et al, 2004, Oh, Ha, Lee et al, 2011, Presta, Tassone, Andreozzi et al, 2011). …”

Section: Angiotensin II and Pathway-selective Insulin Resistance Imentioning

confidence: 99%

“…Ang II impairs the activity and interaction of these critical nodes in the endothelium. Treatment of bovine aortic endothelial cells with Ang II decreases the number of insulin receptors (IR) in the membrane (Oh et al, 2011). Although, the intracellular mechanisms mediating the reduction in IR are yet to be elucidated, this effect was reversed by ATR blocker.…”

Section: Angiotensin II and Pathway-selective Insulin Resistance Imentioning

confidence: 99%

Metabolic actions of angiotensin II and insulin: A microvascular endothelial balancing act

Muniyappa

Yavuz

2013

Molecular and Cellular Endocrinology

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Metabolic actions of insulin to promote glucose disposal are augmented by nitric oxide (NO)-dependent increases in microvascular blood flow to skeletal muscle. The balance between NO-dependent vasodilator actions and endothelin-1-dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. Angiotensin II acting on AT2 receptor increases capillary blood flow to increase insulin-mediated glucose disposal. In contrast, AT1 receptor activation leads to reduced NO bioavailability, impaired insulin signaling, vasoconstriction, and insulin resistance. Insulin-resistant states are characterized by dysregulated local renin-angiotensin-aldosterone system (RAAS). Under insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Similarly, excess AT1 receptor activity in the microvasculature may selectively impair vasodilation while simultaneously potentiating the vasoconstrictor actions of insulin. Therapeutic interventions that target pathway-selective impairment in insulin signaling and the imbalance in AT1 and AT2 receptor signaling in microvascular endothelium may simultaneously ameliorate endothelial dysfunction and insulin resistance. In the present review, we discuss molecular mechanisms in the endothelium underlying microvascular and metabolic actions of insulin and Angiotensin II, the mechanistic basis for microvascular endothelial dysfunction and insulin resistance in RAAS dysregulated clinical states, and the rationale for therapeutic strategies that restore the balance in vasodilator and constrictor actions of insulin and Angiotensin II in the microvasculature.

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“…For example, Ang II can decrease the number of insulin receptors in the membrane in bovine aortic endothelial cells. 33 Ang II leads to phosphorylation of insulin receptor substrates at Ser 636/639 through activating mTOR/p70S6K and inhibits the insulin-stimulated phosphorylation of eNOS via AT 1 R. 34 Insulin-induced capillary recruitment is abrogated, and glucose disposal is attenuated after the treatment with AT 2 R antagonist, PD123319. 35 However, correlation between AT 2 R and insulin receptor on sodium transport in kidney remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells

Yang

Chen

et al. 2018

Journal of the American Society of Hypertension

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Both renin-angiotensin systems and insulin participate in kidney-involved blood pressure regulation. Activation of angiotensin II type 2 receptor (ATR) decreases sodium reabsorption in renal proximal tubule (RPT) cells, whereas insulin produces the opposite effect. We presume that ATR has an inhibitory effect on insulin receptor expression in RPT cells, which may affect renal sodium transport and therefore be of physiological or pathological significance. Our present study found that activation of ATR inhibited insulin receptor expression in a concentration and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. In the presence of a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19-31, 10 mol/L) or a phosphatidylinositol 3 kinase inhibitor (wortmannin, 10 mol/L), the inhibitory effect of ATR on insulin receptor was blocked, indicating that both PKC and phosphatidylinositol 3 kinase were involved in the signaling pathway. There was a linkage between ATR and insulin receptor which was determined by both laser confocal microscopy and coimmunoprecipitation. However, the effect of ATR activation on insulin receptor expression was different in RPT cells from spontaneously hypertensive rats (SHRs). Being contrary to the effect in WKY RPT cells, ATR stimulation increased insulin receptor in SHR RPT cells. Insulin (10 mol/L, 15 minutes) enhanced Na-K-ATPase activity in both WKY and SHR RPT cells. Pretreatment with CGP42112 decreased the stimulatory effect of insulin on Na-K-ATPase activity in WKY RPT cells, whereas pretreatment with CGP42112 increased it in SHR RPT cells. It is suggested that activation of ATR inhibits insulin receptor expression and function in RPT cells. The lost inhibitory effect of ATR on insulin receptor expression may contribute to the pathophysiology of hypertension.

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Angiotensin II Inhibits Insulin Binding to Endothelial Cells

Cited by 9 publications

References 18 publications

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Metabolic actions of angiotensin II and insulin: A microvascular endothelial balancing act

Angiotensin II type 2 receptor inhibits expression and function of insulin receptor in rat renal proximal tubule cells

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