Oxidized Low-Density Lipoproteins Impair Endothelial Function by Inhibiting Non-Genomic Action of Thyroid Hormone–Mediated Nitric Oxide Production in Human Endothelial Cells

Vicinanza, Roberto; Coppotelli, Giuseppe; Malacrino, Carolina; Nardò, Tiziana; Buchetti, Barbara; Lenti, Luisa; Celi, Francesco S.; Scarpa, Susanna

doi:10.1089/thy.2011.0524

Cited by 37 publications

(15 citation statements)

References 41 publications

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“…2009; Vicinanza et al, 2013). Moreover, THs play a significant role in the differentiation of the vast majority of somatic cells (Obregon, 2008;Sirakov et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

López-Noriega

Cobo-Vuilleumier

Narbona-Pérez

et al. 2017

British J Pharmacology

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Thyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation on glucose homeostasis. EXPERIMENTAL APPROACHC57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were killed. The effects of levothyroxine supplementation on metabolic health were determined. C57BL/6 mice treated with levothyroxine for 2 weeks and then challenged with streptozotocin to monitor survival. Mechanistic experiments were conducted in the pancreas, liver and skeletal muscle. RIP-B7.1 mice were treated with levothyroxine for 2 weeks and were subsequently immunized to trigger experimental autoimmune diabetes (EAD). Metabolic tests were performed. Mice were killed and metabolic tissues were extracted for immunohistological analyses. KEY RESULTSLong-term levothyroxine supplementation enhanced glucose clearance and reduced circulating glucose in C57BL/6 mice. Levothyroxine increased simultaneously the proliferation and apoptosis of pancreatic beta cells, promoting the maintenance of a highly insulin-expressing beta cell population. Levothyroxine increased circulating insulin levels, inducing sustained activation of IRS1-AKT signalling in insulin-target tissues. Levothyroxine-treated C57BL/6 mice challenged with streptozotocin exhibited extended survival. Levothyroxine blunted the onset of EAD in RIP-B7.1 mice by inducing beta cell proliferation and preservation of insulin-expressing cells. CONCLUSIONS AND IMPLICATIONSInterventions based on the use of thyroid hormones or thyromimetics could be explored to provide therapeutic benefit in patients with type 1 diabetes mellitus.

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“…2009; Vicinanza et al, 2013). Moreover, THs play a significant role in the differentiation of the vast majority of somatic cells (Obregon, 2008;Sirakov et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

López-Noriega

Cobo-Vuilleumier

Narbona-Pérez

et al. 2017

British J Pharmacology

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“…Previous reports have described different mechanisms of TH action in which T3 binds to cytoplasmic TR and interacts with p85α, the regulatory subunit of PI3K, to activate PI3K and its downstream Akt signaling cascade (Cao et al, 2005;Storey et al, 2002;Vicinanza et al, 2013). Recently, binding of T3 to membrane-localized TR was shown to activate extracellular signal-regulated kinase (ERK) and Akt signaling (Cao et al, 2005;Martin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Adiponectin and Serine/Threonine Kinase Akt Modulation by Triiodothyronine and/or LY294002 in 3T3‐L1 Adipocytes

Oliveira

Rodrigues

Olímpio

et al. 2019

Lipids

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Adipose tissue (AT), an endocrine organ that modulates several physiological functions by synthesizing and releasing adipokines such as adiponectin, is a metabolic target of triiodothyronine (T3). T3 and adiponectin play important roles in controlling normal metabolic functions such as stimulation of fatty acid oxidation and increase in thermogenesis. The phosphatidylinositol 3‐kinase (PI3K) pathway is important for the differentiation of preadipocytes into adipocytes and can be activated by T3 for the transcription of specific genes, such as adiponectin. We examined the role of PI3K in adiponectin modulation by T3 action in murine adipocytes (3T3‐L1). The 3T3‐L1 adipocytes were treated with 1000 nM T3 for 1 h in the presence or absence of 50 μM LY294002 (LY), a PI3K inhibitor. Then, we assessed the expression of adiponectin and the phosphorylated serine/threonine kinase Akt (pAkt), a PI3K signaling protein, in the adipocytes. Adiponectin and pAKT levels were higher in the T3‐adipocyte cells, whereas in the LY group adiponectin was elevated and pAKT was decreased compared to the control (C). PI3K pathway inhibition for 1 h and posterior treatment with T3, in LY + T3, reduced the adiponectin level and increased pAKT levels compared to those in LY. T3 stimulated adiponectin levels by PI3K pathway activation and T3 can compensate alteration in the PI3K pathway, because with inhibition of the pathway it is able to maintain the basal levels of adiponectin and pAKT.

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“…Moreover endothelial Nitric Oxide (NO) can regulate dilatation of blood vessels and that decreased NO availability is related to endothelial dysfunction [21,22]. Vicinanza R et al reported that the process of endothelial NO production could be mediated by TH [23]. Hence, THs protect the endothelial cells of micro-vessels from degeneration, which may be the reliable evidence for supporting our main conclusion as follow: FT3 could be positively correlated with certain NCSs parameters in patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

The Association Between the Levels of Thyroid Hormones and Peripheral Nerve Conduction in Patients with Type 2 Diabetes Mellitus

Zhu

Yang

2018

Exp Clin Endocrinol Diabetes

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Oxidized Low-Density Lipoproteins Impair Endothelial Function by Inhibiting Non-Genomic Action of Thyroid Hormone–Mediated Nitric Oxide Production in Human Endothelial Cells

Cited by 37 publications

References 41 publications

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

Adiponectin and Serine/Threonine Kinase Akt Modulation by Triiodothyronine and/or LY294002 in 3T3‐L1 Adipocytes

The Association Between the Levels of Thyroid Hormones and Peripheral Nerve Conduction in Patients with Type 2 Diabetes Mellitus

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