scholarly journals Adiponectin regulates glycogen metabolism at the human fetal–maternal interface

2018 ◽  
Vol 61 (3) ◽  
pp. 139-152 ◽  
Author(s):  
Fabien Duval ◽  
Esther Dos Santos ◽  
Benoît Maury ◽  
Valérie Serazin ◽  
Khadija Fathallah ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
Critical Role ◽  
Glycogen Metabolism ◽  
First Trimester ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Glycogen Accumulation ◽  
First Trimester Of Pregnancy

Throughout the entire first trimester of pregnancy, fetal growth is sustained by endometrial secretions, i.e. histiotrophic nutrition. Endometrial stromal cells (EnSCs) accumulate and secrete a variety of nutritive molecules that are absorbed by trophoblastic cells and transmitted to the fetus. Glycogen appears to have a critical role in the early stages of fetal development, since infertile women have low endometrial glycogen levels. However, the molecular mechanisms underlying glycogen metabolism and trafficking at the fetal–maternal interface have not yet been characterized. Among the various factors acting at the fetal–maternal interface, we focused on adiponectin – an adipocyte-secreted cytokine involved in the control of carbohydrate and lipid homeostasis. Our results clearly demonstrated that adiponectin controls glycogen metabolism in EnSCs by (i) increasing glucose transporter 1 expression, (ii) inhibiting glucose catabolism via a decrease in lactate and ATP productions, (iii) increasing glycogen synthesis, (iv) promoting glycogen accumulation via phosphoinositide-3 kinase activation and (v) enhancing glycogen secretion. Furthermore, our results revealed that adiponectin significantly limits glycogen endocytosis by human villous trophoblasts. Lastly, we demonstrated that once glycogen has been endocytosed into placental cells, it is degraded into glucose molecules in lysosomes. Taken as a whole, the present results demonstrate that adiponectin exerts a dual role at the fetal–maternal interface by promoting glycogen synthesis in the endometrium and conversely reducing trophoblastic glycogen uptake. We conclude that adiponectin may be involved in feeding the conceptus during the first trimester of pregnancy by controlling glycogen metabolism in both the uterus and the placenta.

Influence of glucose metabolism on vascular smooth muscle cell proliferation

VASA ◽  
2013 ◽  
Vol 42 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Mario Chiong ◽  
Pablo E. Morales ◽  
Gloria Torres ◽  
Tomás Gutiérrez ◽  
Lorena García ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Glucose Metabolism ◽  
Vascular Smooth Muscle ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Critical Role ◽  
Small Gtpase ◽  
Mitofusin 2 ◽  
Glucose Transporter 1 ◽  
Vsmc Proliferation

Differentiation of vascular smooth muscle cells (VSMC) is an essential process of vascular development. VSMC have biosynthetic, proliferative, and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMC play a critical role in the pathogenesis of atherosclerosis and intimal hyperplasia, as well as in a variety of other human diseases, including hypertension, asthma, atherosclerosis and vascular aneurysm. This review provides an overview of the current state of knowledge of molecular mechanisms involved in controlling VSMC proliferation, with particular focus on glucose metabolism and its relationship with mitochondrial bioenergetics. Increased levels of glucose transporter 1 (GLUT1) are observed in VSMC after endothelial injury, suggesting a relationship between glucose uptake and VSMC proliferation. Mitochondrial dysfunction is a common feature in VSMC during atherosclerosis. Alterations in mitochondrial function can be produced by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion. Moreover, exacerbated proliferation was observed in VSMC from pulmonary arteries with hyperpolarized mitochondria and enhanced glycolysis/glucose oxidation ratio. Several lines of evidence highlight the relevance of glucose metabolism in the control of VSMC proliferation, indicating a new area to be explored in the control of vascular pathogenesis.

scholarly journals Storage and Utilization of Glycogen by Mouse Liver during Adaptation to Nutritional Changes Are GLP-1 and PASK Dependent

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2552
Author(s):  
Ana Pérez-García ◽  
Verónica Hurtado-Carneiro ◽  
Carmen Herrero-De-Dios ◽  
Pilar Dongil ◽  
José Enrique García-Mauriño ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Energy Homeostasis ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Regulatory Element ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Hepatic Glycogen ◽  
Glycogen Accumulation ◽  
Glucose Transporter 2

Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.

scholarly journals Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism inNeurospora crassa

2019 ◽  
Vol 116 (21) ◽  
pp. 10435-10440 ◽  
Author(s):  
Mokryun Baek ◽  
Stela Virgilio ◽  
Teresa M. Lamb ◽  
Oneida Ibarra ◽  
Juvana Moreira Andrade ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Cellular Functions ◽  
Glycogen Accumulation ◽  
Homeostatic Process ◽  
Allosteric Control ◽  
Clock Component

Circadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, inNeurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that whilegsnwas necessary for glycogen production, constitutivegsnexpression resulted in high and arrhythmic glycogen levels, and deletion ofgpnabolishedgsnmRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show thatgsnpromoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmicgsnmRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulatedgsntranscription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis.

scholarly journals Glucose transporter 1 is important for the glycolytic metabolism of human endometrial stromal cells in hypoxic environment

Heliyon ◽  
2020 ◽  
Vol 6 (6) ◽  
pp. e03985
Author(s):  
Takeharu Kido ◽  
Hiromi Murata ◽  
Akemi Nishigaki ◽  
Hiroaki Tsubokura ◽  
Shinnosuke Komiya ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Glucose Transporter ◽  
Glycolytic Metabolism ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Hypoxic Environment

scholarly journals Antidiabetic Activities ofAbutilon indicum(L.) Sweet Are Mediated by Enhancement of Adipocyte Differentiation and Activation of the GLUT1 Promoter

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Chutwadee Krisanapun ◽  
Seong-Ho Lee ◽  
Penchom Peungvicha ◽  
Rungravi Temsiririrkkul ◽  
Seung Joon Baek
Keyword(s):  
Crude Extract ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Adipocyte Differentiation ◽  
Glucose Consumption ◽  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
Glucose Transporter 1 ◽  
Postprandial Plasma Glucose ◽  
Insulin Like Activity

Abutilon indicum(L.) Sweet is an Asian phytomedicine traditionally used to treat several disorders, including diabetes mellitus. However, molecular mechanisms supporting the antidiabetic effect ofA. indicumL. remain unknown. The aim of this study was to evaluate whether extract ofA. indicumL. improves insulin sensitivity. First, we observed the antidiabetic activity of aqueous extract of the entire plant (leaves, twigs and roots) ofA. indicumL. on postprandial plasma glucose in diabetic rats. The subsequent experiments revealed that butanol fractions of the extract bind to PPARγand activate 3T3-L1 differentiation. To measure glucose uptake enhanced by insulin-like activity, we used rat diaphragm incubated with various concentrations of the crude extract and found that the extract enhances glucose consumption in the incubated solution. Our data also indicate that the crude extract and the fractions (water and butanol) did not affect the activity of kinases involved in Akt and GSK-3βpathways; however, the reporter assay showed that the crude extract could activate glucose transporter 1 (GLUT1) promoter activity. These results suggest that the extract fromA. indicumL. may be beneficial for reducing insulin resistance through its potency in regulating adipocyte differentiation through PPARγagonist activity, and increasing glucose utilization via GLUT1.

scholarly journals Heating after intense repeated contractions inhibits glycogen accumulation in mouse EDL muscle: role of phosphorylase in postexercise glycogen metabolism

2018 ◽  
Vol 315 (5) ◽  
pp. C706-C713 ◽  
Author(s):  
Sarah J. Blackwood ◽  
Ester Hanya ◽  
Abram Katz
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Type Ii ◽  
Muscle Type ◽  
Phosphorylase Activity ◽  
Glycogen Accumulation ◽  
Longus Muscle ◽  
Edl Muscle

The effects of heating on glycogen synthesis (incorporation of [14C]glucose into glycogen) and accumulation after intense repeated contractions were investigated. Isolated mouse extensor digitorum longus muscle (type II) was stimulated electrically to perform intense tetanic contractions at 25°C. After 120 min recovery at 25°C, glycogen accumulated to almost 80% of basal, whereas after recovery at 35°C, glycogen remained low (~25% of basal). Glycogen synthesis averaged 0.97 ± 0.07 µmol·30 min−1·g wet wt−1 during recovery at 25°C and 1.48 ± 0.08 during recovery at 35°C ( P < 0.001). There were no differences in phosphorylase and glycogen synthase total activities nor in phosphorylase fractional activity, whereas glycogen synthase fractional activity was increased by ~50% after recovery at 35°C vs. 25°C. Inorganic phosphate (Pi, substrate for phosphorylase) was markedly increased (~300% of basal) following contraction but returned to control levels after 120 min recovery at 25°C. In contrast, Pi remained elevated after recovery at 35°C (>2-fold higher than recovery at 25°C). Estimates of glycogen breakdown indicated that phosphorylase activity (either via inhibition at 25°C or activation at 35°C) was responsible for ~60% of glycogen accumulation during recovery at 25°C and ~45% during recovery at 35°C. These data demonstrate that despite the enhancing effect of heating on glycogen synthesis during recovery from intense contractions, glycogen accumulation is inhibited owing to Pi-mediated activation of phosphorylase. Thus phosphorylase can play a quantitatively important role in glycogen biogenesis during recovery from repeated contractions in isolated type II muscle.

scholarly journals Identification and application of plasmatic microRNA expression quantitative trait loci (miR-QTL) at first trimester of pregnancy

2021 ◽  
Author(s):  
Frédérique White ◽  
Marika Groleau ◽  
Samuel Côté ◽  
Cécilia Légaré ◽  
Kathrine Thibeault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait Loci ◽  
Instrumental Variables ◽  
Quantitative Trait ◽  
Molecular Mechanisms ◽  
First Trimester ◽  
Risk Scores ◽  
Expression Quantitative Trait Loci ◽  
Trait Loci ◽  
First Trimester Of Pregnancy

AbstractBackgroundMicroRNAs (miRNAs) are a class of small non-coding RNAs regulating gene expression. They are involved in many biological processes, including adaptation to pregnancy. The identification of genetic variants associated with gene expression, known as expression quantitative trait loci (eQTL), helps to understand the underlying molecular mechanisms and determinants of complex diseases. Using data from the prospective pre-birth Gen3G cohort, we investigated associations between maternal genotypes and plasmatic miRNA levels measured during the first trimester of pregnancy of 369 women.ResultsAssessing the associations between about 2 million SNPs and miRNA proximal pairs using best practices from the GTEx consortium, a total of 22,140 significant eQTLs involving 147 unique miRNAs were identified. Elastic-net regressions were applied to select the most relevant SNPs to build genetic risk scores (GRS) for each of these 147 miRNAs. For about half of the circulating miRNAs, the GRS captured >10% of the variance abundance. As a demonstration of the usefulness of the identified eQTLs and derived GRS, we used the GRSs as instrumental variables to test for association between the circulating levels of miRNAs quantified before the 16th week of pregnancy and the development of pregnancy complications (gestational diabetes [GDM] or pre-eclampsia [PE]) developing more than three months later on average. Using predicted miRNA levels derived from instrumental variables, we found 18 significant associations of miRNAs with potential support of causal inference for GDM or PE.ConclusionsOur results represent a valuable resource to understand miRNA regulation and highlight the potential of genetic instruments in predicting circulating miRNA levels and their possible contribution in disease development.

scholarly journals Insulin regulation of solute carrier family 2 member 1 (glucose transporter 1) expression and glucose uptake in decidualizing human endometrial stromal cells: an in vitro study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ivika Jakson ◽  
Dorina Ujvari ◽  
Sebastian Brusell Gidlöf ◽  
Angelica Lindén Hirschberg
Keyword(s):  
Glucose Uptake ◽  
Stromal Cells ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Solute Carrier Family ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Protein Levels ◽  
Solute Carrier

Abstract Background Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells. Methods We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett’s multiple comparisons test and paired t-test were used to determine the statistical significance of the results. Results We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations. Conclusions These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.

scholarly journals Dehydroepiandrosterone Inhibits Glucose Flux Through the Pentose Phosphate Pathway in Human and Mouse Endometrial Stromal Cells, Preventing Decidualization and Implantation

2011 ◽  
Vol 25 (8) ◽  
pp. 1444-1455 ◽  
Author(s):  
Antonina I. Frolova ◽  
Kathleen O'Neill ◽  
Kelle H. Moley
Keyword(s):  
Stromal Cells ◽  
Pentose Phosphate Pathway ◽  
Glucose Transporter ◽  
Polycystic Ovary ◽  
Pentose Phosphate ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Decidual Cells

Endometrial stromal cells (ESC) must undergo a hormone-driven differentiation to form decidual cells as a requirement of proper embryo implantation. Recent studies from our laboratory have demonstrated that decidualizing cells require glucose transporter 1 expression and an increase in glucose use to complete this step. The present study focuses on the glucose-dependent molecular and metabolic pathways, which are required by ESC for decidualization. Inhibition of glycolysis had no effect on decidualization. However, blockade of the pentose phosphate pathway (PPP) with pharmacologic inhibitors 6-aminonicotinamide or dehydroepiandrosterone (DHEA), and short hairpin RNA-mediated knockdown of glucose-6-phosphate dehydrogenase, the rate-limiting step in the PPP, both led to strong decreases in decidual marker expression in vitro and decreased decidualization in vivo. Additionally, the studies demonstrate that inhibition is due, at least in part, to ribose-5-phosphate depletion, because exogenous nucleoside administration restored decidualization in these cells. The finding that PPP inhibition prevents decidualization of ESC is novel and clinically important, because DHEA is an endogenous hormone produced by the adrenal glands and elevated in a high proportion of women who have polycystic ovary syndrome, the most common endocrinopathy in reproductive age women. Together, this data suggest a mechanistic link between increased DHEA levels, use of glucose via the PPP, and pregnancy loss.

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