scholarly journals β3-Adrenergic Receptors Stimulate Glucose Uptake in Brown Adipocytes by Two Mechanisms Independently of Glucose Transporter 4 Translocation

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5730-5739 ◽  
Author(s):  
O. S. Dallner ◽  
E. Chernogubova ◽  
K. A. Brolinson ◽  
T. Bengtsson
Keyword(s):  
Glucose Uptake ◽  
Adrenergic Receptors ◽  
Glucose Transporter ◽  
Glucose Transporter 4 ◽  
Brown Adipocytes

Abstract 235: Sarcolemmal Membrane Associated Protein Isoform 1: a Unique Regulator of Glucose Uptake and Metabolism in the Myocardium

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Aaraf Dewan ◽  
Maysoon Salih ◽  
Christopher Triggle ◽  
Hong Ding ◽  
Balwant Tuana
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glucose Transporter 4 ◽  
Specific Expression ◽  
Western Blots ◽  
Sarcolemmal Membrane ◽  
Neonatal Cardiomyocytes ◽  
Early Endosomes ◽  
Protein Isoform ◽  
Uptake And Metabolism

As one of the leading causes of heart disease, diabetes is a problem which needs a solution. Regulation of glucose uptake and metabolism within skeletal and cardiac muscle has proven capable of altering systemic glucose levels and impacting metabolism to potentially improve patient outcomes. Unfortunately, to date, very few muscle specific metabolic regulators are known which can allow us to achieve blood glucose uptake and metabolism. Sarcolemmal Membrane Associated Protein Isoform 1 (SLMAP1) is a novel protein expressed predominantly within muscle tissue. It has been linked to diabetes through animal models, although its role in metabolism remains to be defined. Here we describe a novel role for SLMAP1 in glucose metabolism within the myocardium. We engineered a transgenic (TG) mouse with cardiac specific expression of SLMAP1. Using neonatal cardiomyocytes (NCMs) collected from these mice we performed glucose uptake assays with 2-deoxy-glucose (2DG), measured glycolytic rate using an Extracellular Flux XF24e Bioanalyzer, and analyzed glucose transporter 4 (GLUT4) trafficking using Western Blots, qPCR, and immunofluorescence imaging. NCMs extracted from TG hearts expressing SLMAP1 displayed increased levels of 2DG uptake (93% ± 25%, n=5, P<0.01), basal glycolysis (glycolysis (92 ± 40%, n=5, P<0.05), and maximal glycolysis (75 ± 31%, n=5, P<0.05) compared with wildtype littermates. Confocal microscopy revealed both increased localization of glucose transporter 4 (GLUT4) at the cell surface as well as an expansion of GLUT4 early endosomes in TG NCMs. The data here indicates SLMAP1 as a novel regulator of glucose uptake and metabolism in the myocardium. The targeted expression of SLMAP1 in a muscle specific manner may enhance systemic glycemic control and serve to limit cardiovascular disease in metabolic disorders such as diabetes.

scholarly journals Artemisia princeps Extract Promoted Glucose Uptake in Cultured L6 Muscle Cells via Glucose Transporter 4 Translocation

2010 ◽  
Vol 74 (10) ◽  
pp. 2036-2042 ◽  
Author(s):  
Norio YAMAMOTO ◽  
Manabu UEDA ◽  
Kyuichi KAWABATA ◽  
Takuya SATO ◽  
Kengo KAWASAKI ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Glucose Transporter 4 ◽  
Artemisia Princeps ◽  
L6 Muscle Cells

scholarly journals Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin

1996 ◽  
Vol 314 (2) ◽  
pp. 485-490 ◽  
Author(s):  
Yasutake SHIMIZU ◽  
Danuta KIELAR ◽  
Yasuhiko MINOKOSHI ◽  
Takashi SHIMAZU
Keyword(s):  
Cyclic Amp ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Sympathetic Nerves ◽  
Intrinsic Activity ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Km Value ◽  
Glucose Transporter Glut4

Glucose uptake into brown adipose tissue has been shown to be enhanced directly by noradrenaline (norepinephrine) released from sympathetic nerves. In this study we characterized the glucose transport system in cultured brown adipocytes, which responds to noradrenaline as well as insulin, and analysed the mechanism underlying the noradrenaline-induced increase in glucose transport. Insulin increased 2-deoxyglucose (dGlc) uptake progressively at concentrations from 10-11 to 10-6 M, with maximal stimulation at 10-7 M. Noradrenaline concentrations ranging from 10-8 to 10-6 M also enhanced dGlc uptake, even in the absence of insulin. The effects of noradrenaline and insulin on dGlc uptake were additive. The stimulatory effect of noradrenaline was mimicked by the β3-adrenergic agonist, BRL37344, at concentrations two orders lower than noradrenaline. Dibutyryl cyclic AMP also mimicked the stimulatory effect of noradrenaline, and the antagonist of cyclic AMP, cyclic AMP-S Rp-isomer, blocked the enhancement of glucose uptake due to noradrenaline. Furthermore Western blot analysis with an anti-phosphotyrosine antibody revealed that, in contrast with insulin, noradrenaline apparently does not stimulate intracellular phosphorylation of tyrosine, suggesting that the noradrenaline-induced increase in dGlc uptake depends on elevation of the intracellular cyclic AMP level and not on the signal chain common to insulin. When cells were incubated with insulin, the content of the muscle/adipocyte type of glucose transporter (GLUT4) in the plasma membrane increased, with a corresponding decrease in the amount in the microsomal membrane. In contrast, noradrenaline did not affect the subcellular distribution of GLUT4 or that of the HepG2/erythrocyte type of glucose transporter. Although insulin increased Vmax. and decreased the Km value for glucose uptake, the effect of noradrenaline was restricted to a pronounced decrease in Km. These results suggest that the mechanism by which noradrenaline stimulates glucose transport into brown adipocytes is not due to translocation of GLUT but is probably due to an increase in the intrinsic activity of GLUT, which is mediated by a cyclic AMP-dependent pathway.

scholarly journals Glucose Transporter-4 Facilitates Insulin-Stimulated Glucose Uptake in Osteoblasts

Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4094-4103 ◽  
Author(s):  
Zhu Li ◽  
Julie L. Frey ◽  
G. William Wong ◽  
Marie-Claude Faugere ◽  
Michael J. Wolfgang ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glucose Transporter 4

scholarly journals Effect of Litsea lancifolia leaf extract on glucose transporter 4 translocation and glucose uptake in 3T3L1 cell line

2019 ◽  
Vol 11 (3) ◽  
pp. 240
Author(s):  
SurapaneniKrishna Mohan ◽  
Murad Alsawalha ◽  
AbeerMohammed Al-Subaie ◽  
ReemYousuf Al-Jindan ◽  
SrinivasaRao Bolla ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Cell Line ◽  
Leaf Extract ◽  
Glucose Transporter ◽  
Glucose Transporter 4 ◽  
3T3l1 Cell

scholarly journals High levels of chorionic gonadotrophin attenuate insulin sensitivity and promote inflammation in adipocytes

2015 ◽  
Vol 54 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Qinyun Ma ◽  
Jianxia Fan ◽  
Jiqiu Wang ◽  
Shuai Yang ◽  
Qing Cong ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Chorionic Gonadotrophin ◽  
Nuclear Factor ◽  
Glucose Transporter 4 ◽  
Chemotactic Protein ◽  
Impaired Insulin ◽  
Low Levels ◽  
Light Chain Enhancer

Gestational diabetes mellitus (GDM) presents with moderate inflammation, insulin resistance and impaired glucose uptake, which may result from increased maternal fat mass and increased circulation of placental hormones and adipokines. In this study, we set out to test whether the surge in chorionic gonadotrophin (CG) secretion is a cause of inflammation and impaired insulin sensitivity in GDM. We first found that LH/chorionic gonadotrophin receptors (CG/LHR) were expressed at low levels in insulin-sensitive murine 3T3-L1 adipocytes and murine C2C12 myocytes. CG treatment not only directly reduced insulin-responsive gene expression, including that of glucose transporter 4 (GLUT4), but also impaired insulin-stimulated glucose uptake in 3T3-L1 cells. Moreover, CG treatment increased the expression of the proinflammatory cytokine monocyte chemotactic protein 1 (MCP1) and upregulated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in 3T3-L1 cells. Clinically, pregnant women who had higher CG levels and elevated MCP1 developed GDM. Above all, apart from prepregnancy BMI and MCP1 level, CG level was associated with abnormal glucose tolerance. In summary, our findings confirmed that higher CG levels in pregnancy possibly played a role in GDM development partly by impairing the functions of insulin, such those involved in as glucose uptake, while promoting inflammation in adipocyte.

scholarly journals An Inositol 1,4,5-Triphosphate (IP3)-IP3 Receptor Pathway Is Required for Insulin-Stimulated Glucose Transporter 4 Translocation and Glucose Uptake in Cardiomyocytes

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4665-4677 ◽  
Author(s):  
A. E. Contreras-Ferrat ◽  
B. Toro ◽  
R. Bravo ◽  
V. Parra ◽  
C. Vásquez ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Green Fluorescent Protein ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Enhanced Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Glucose Transporter 4 ◽  
Ip3 Receptor ◽  
Phosphatidylinositol 3 Kinase ◽  
Green Fluorescent

Intracellular calcium levels ([Ca2+]i) and glucose uptake are central to cardiomyocyte physiology, yet connections between them have not been studied. We investigated whether insulin regulates [Ca2+]i in cultured cardiomyocytes, the participating mechanisms, and their influence on glucose uptake via SLC2 family of facilitative glucose transporter 4 (GLUT4). Primary neonatal rat cardiomyocytes were preloaded with the Ca2+ fluorescent dye fluo3-acetoxymethyl ester compound (AM) and visualized by confocal microscopy. Ca2+ transport pathways were selectively targeted by chemical and molecular inhibition. Glucose uptake was assessed using [3H]2-deoxyglucose, and surface GLUT4 levels were quantified in nonpermeabilized cardiomyocytes transfected with GLUT4-myc-enhanced green fluorescent protein. Insulin elicited a fast, two-component, transient increase in [Ca2+]i. Nifedipine and ryanodine prevented only the first component. The second one was reduced by inositol-1,4,5-trisphosphate (IP3)-receptor-selective inhibitors (xestospongin C, 2 amino-ethoxydiphenylborate), by type 2 IP3 receptor knockdown via small interfering RNA or by transfected Gβγ peptidic inhibitor βARKct. Insulin-stimulated glucose uptake was prevented by bis(2-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid-AM, 2-amino-ethoxydiphenylborate, and βARK-ct but not by nifedipine or ryanodine. Similarly, insulin-dependent exofacial exposure of GLUT4-myc-enhanced green fluorescent protein was inhibited by bis(2-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid-AM and xestospongin C but not by nifedipine. Phosphatidylinositol 3-kinase and Akt were also required for the second phase of Ca2+ release and GLUT4 translocation. Transfected dominant-negative phosphatidylinositol 3-kinase γ inhibited the latter. In conclusion, in primary neonatal cardiomyocytes, insulin induces an important component of Ca2+ release via IP3 receptor. This component signals to glucose uptake via GLUT4, revealing a so-far unrealized contribution of IP3-sensitive Ca2+ stores to insulin action. This pathway may influence cardiac metabolism in conditions yet to be explored in adult myocardium.

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