Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Roos, Sara; Lagerlöf, Olof; Wennergren, Margareta; Powell, Theresa L.; Jansson, Thomas

doi:10.1152/ajpcell.00191.2009

Cited by 146 publications

(153 citation statements)

References 64 publications

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“…The MTOR signaling influences the activity of members of several transport systems (e.g. System L, A, and Taut), modulates translation, and influences in this manner AA uptake in the placenta (Roos et al 2009). We suggest a regulatory effect of MTOR on AA transport in maternal and conceptus tissues during the preimplantation period.…”

Section: Discussionmentioning

confidence: 99%

Increase of essential amino acids in the bovine uterine lumen during preimplantation development

Groebner

Rubio‐Aliaga²,

Schülke³

et al. 2011

Reproduction

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Amino acids (AAs) are crucial for the developing conceptus prior to implantation. To provide insights into the requirements of the bovine embryo, we determined the AA composition of the uterine fluid. At days 12, 15, and 18 post-estrus, the uteri of synchronized pregnant and non-pregnant Simmental heifers were flushed for the analysis of 41 AAs and their derivatives by liquid chromatography-tandem mass spectrometry. The ipsilateral endometrium was sampled for quantitative PCR. In addition to a pregnancy-dependent increase of the essential AAs (P!0.01), we detected elevated concentrations for most non-essential proteinogenic AAs. Histidine (His) and the expression of the His/peptide transporter solute carrier 15A3 (SLC15A3) were significantly increased at day 18 of pregnancy in vivo. In addition, SLC15A3 was predominantly stimulated by trophoblast-derived interferon-t in stroma cells of an in vitro co-culture model of endometrial cells. Our results show an increased concentration of AAs most likely to optimally provide the elongating pre-attachment conceptus with nutrients.

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Section: Discussionmentioning

confidence: 99%

Increase of essential amino acids in the bovine uterine lumen during preimplantation development

Groebner

Rubio‐Aliaga²,

Schülke³

et al. 2011

Reproduction

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“…L-and A-type systems are sensitive to mTORC1 activation, which in turn may be activated by insulin and other growth factors (Roos et al 2009, Drummond et al 2010. In mammalian cells, mTORC1 is essential for the phosphorylation and activation of S6K1, which directly impacts cell growth via eukaryotic initiation factor translation complexes .…”

Section: Nutrient Metabolism and Insulin Action In Target Tissuesmentioning

confidence: 99%

Nutrient regulation of insulin secretion and action

Newsholme

Cruzat

Keane

2014

Journal of Endocrinology

186

128

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Pancreatic b-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The b-cell is an intricately designed cell type that couples metabolism of dietary sources of carbohydrates, amino acids and lipids to insulin secretory mechanisms, such that insulin release occurs at appropriate times to ensure efficient nutrient uptake and storage by target tissues. However, chronic exposure to high nutrient concentrations results in altered metabolism that impacts negatively on insulin exocytosis, insulin action and may ultimately lead to development of DM. Reduced action of insulin in target tissues is associated with impairment of insulin signalling and contributes to insulin resistance (IR), a condition often associated with obesity and a major risk factor for DM. The altered metabolism of nutrients by insulin-sensitive target tissues (muscle, adipose tissue and liver) can result in high circulating levels of glucose and various lipids, which further impact on pancreatic b-cell function, IR and progression of the metabolic syndrome. Here, we have considered the role played by the major nutrient groups, carbohydrates, amino acids and lipids, in mediating b-cell insulin secretion, while also exploring the interplay between amino acids and insulin action in muscle. We also focus on the effects of altered lipid metabolism in adipose tissue and liver resulting from activation of inflammatory processes commonly observed in DM pathophysiology. The aim of this review is to describe commonalities and differences in metabolism related to insulin secretion and action, pertinent to the development of DM.

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“…of placental gene expression (48) or via mammalian target of rapamycin signalling (49) . Maternal macronutrients in particular, have been ascribed a strong influence on fetal development.…”

Section: Fetal Developmental Plasticity and Appropriate Epigenetic Chmentioning

confidence: 99%

Early nutrition programming of long-term health

et al. 2012

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Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as 'developmental programming'). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project 'EarlyNutrition'. Currently, three key hypotheses have been defined: the fuel mediated 'in utero' hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental 'mismatch' between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.Early nutrition: Developmental programming: Obesity and related disorders:

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Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Cited by 146 publications

References 64 publications

Increase of essential amino acids in the bovine uterine lumen during preimplantation development

Increase of essential amino acids in the bovine uterine lumen during preimplantation development

Nutrient regulation of insulin secretion and action

Early nutrition programming of long-term health

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