Disruption of Cortical Actin in Skeletal Muscle Demonstrates an Essential Role of the Cytoskeleton in Glucose Transporter 4 Translocation in Insulin-sensitive Tissues

Deletion of glucose transporter geneSlc2a3(GLUT3) has previously been reported to result in embryonic lethality. Here, we define the exact time point of growth arrest and subsequent death of the embryo.Slc2a3−/−morulae and blastocysts developed normally, implantedin vivo, and formed egg-cylinder-stage embryos that appeared normal until day 6.0. At day 6.5, apoptosis was detected in the ectodermal cells ofSlc2a3−/−embryos resulting in severe disorganization and growth retardation at day 7.5 and complete loss of embryos at day 12.5. GLUT3 was detected in placental cone, in the visceral ectoderm and in the mesoderm of 7.5-day-old wild-type embryos. Our data indicate that GLUT3 is essential for the development of early post-implanted embryos.

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Antidiabetic and Antihyperlipidemic Effects ofClitocybe nudaon Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/981046 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Mei-Hsing Chen ◽

Cheng-Hsiu Lin ◽

Chun-Ching Shih

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Glucose Transporter ◽

Body Weight Gain ◽

Glucose Production ◽

Hypolipidemic Effect ◽

Glucose Transporter 4 ◽

High Fat ◽

Hepatic Expression ◽

Amp Activated Protein Kinase

The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract ofClitocybe nuda(CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P<0.001,P<0.01,P<0.05, resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.

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Abstract 112: A Pathological Role of Endothelial p53 in the Regulation of Endothelial Function and Glucose Metabolism

Circulation Research ◽

10.1161/res.113.suppl_1.a112 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Masataka YOKOYAMA ◽

Yoshio KOBAYASHI ◽

Tohru MINAMINO

Keyword(s):

Skeletal Muscle ◽

Endothelial Cell ◽

Glucose Metabolism ◽

Endothelial Function ◽

Mitochondrial Biogenesis ◽

Glucose Transporter ◽

Diabetic Patients ◽

Glucose Transporter 1 ◽

P53 Activation

Cellular senescence is a state of irreversible growth arrest induced by various stresses such as oncogenic stimuli. This response is controlled by negative regulators of the cell cycle like the p53 tumor suppressor protein. Accumulating evidence has suggested a role of p53 activation in various age-associated conditions including atherosclerosis, heart failure and diabetes. Here we show that endothelial p53 activation plays a pathological role in the regulation of endothelial function and glucose metabolism under diabetic conditions. Endothelial expression of p53 was markedly up-regulated in a streptozotocin-induced diabetes model. Endothelial function such as acetylcholine-dependent vasodilatation was markedly impaired in this model. Although hyperglycemia was not altered, impairment of endothelial function was significantly improved in mice with endothelial cell-specific p53 deficiency. In same way, p53 was markedly activated in ischemic vessels, and endothelial p53 deficiency enhanced ischemia-induced angiogenesis. Mechanistically, endothelial p53 up-regulated the expression of PTEN that negatively regulated the Akt-eNOS pathway, and therefore disruption of p53 improved endothelial dysfunction. We also found that endothelial p53 was markedly activated, and the Akt-eNOS pathway was attenuated in a diet-induced obesity model. Disruption of endothelial p53 activation improved dietary inactivation of eNOS that up-regulated the expression of PGC-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Inhibition of endothelial p53 also improved dietary impairment of glucose transport into skeletal muscle by up-regulating endothelial expression of glucose transporter 1. Consequently, mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation compared with control littermates. These results indicate that endothelial p53 negatively regulates endothelium-dependent vasodilatation, ischemia-induced angiogenesis, and mitochondrial biogenesis by inhibiting the Akt-eNOS pathway and suggest that inhibition of endothelial p53 could be a novel therapeutic target in diabetic patients.

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D-Pinitol andmyo-Inositol Stimulate Translocation of Glucose Transporter 4 in Skeletal Muscle of C57BL/6 Mice

Bioscience Biotechnology and Biochemistry ◽

10.1271/bbb.90963 ◽

2010 ◽

Vol 74 (5) ◽

pp. 1062-1067 ◽

Cited By ~ 56

Author(s):

Nhung Thuy DANG ◽

Rie MUKAI ◽

Ken-ichi YOSHIDA ◽

Hitoshi ASHIDA

Keyword(s):

Skeletal Muscle ◽

Glucose Transporter ◽

Glucose Transporter 4

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MicroRNA-15a Inhibits Glucose Transporter 4 Translocation and Impairs Glucose Metabolism in L6 Skeletal Muscle Via Targeting of Vesicle-Associated Membrane Protein-Associated Protein A

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2019.07.151 ◽

2020 ◽

Vol 44 (3) ◽

pp. 261-266.e2

Author(s):

Ying Guo ◽

Gang Li ◽

Huiqing Li ◽

Chunlan Huang ◽

Qiao Liu ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Metabolism ◽

Membrane Protein ◽

Glucose Transporter ◽

Protein A ◽

Glucose Transporter 4

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Triiodothyronine improves age-induced glucose intolerance and increases the expression of sirtuin-1 and glucose transporter-4 in skeletal muscle of aged rats

General Physiology and Biophysics ◽

10.4149/gpb_2018026 ◽

2018 ◽

Vol 37 (06) ◽

pp. 677-686 ◽

Cited By ~ 1

Author(s):

Sahar M. El

Keyword(s):

Skeletal Muscle ◽

Glucose Intolerance ◽

Glucose Transporter ◽

Sirtuin 1 ◽

Aged Rats ◽

Glucose Transporter 4

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Caffeamide 36-13 Regulates the Antidiabetic and Hypolipidemic Signs of High-Fat-Fed Mice on Glucose Transporter 4, AMPK Phosphorylation, and Regulated Hepatic Glucose Production

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/821569 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Yueh-Hsiung Kuo ◽

Cheng-Hsiu Lin ◽

Chun-Ching Shih

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Glucose Transporter ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Hypolipidemic Effect ◽

Glucose Transporter 4 ◽

High Fat ◽

Amide Derivatives ◽

Hepatic Glucose

This study was to investigate the antidiabetic and antihyperlipidemic effects of (E)-3-[3, 4-dihydroxyphenyl-1-(piperidin-1-yl)prop-2-en-1-one] (36-13) (TS), one of caffeic acid amide derivatives, on high-fat (HF-) fed mice. The C57BL/6J mice were randomly divided into the control (CON) group and the experimental group, which was firstly fed a HF diet for 8 weeks. Then, the HF group was subdivided into four groups and was given TS orally (including two doses) or rosiglitazone (Rosi) or vehicle for 4 weeks. Blood, skeletal muscle, and tissues were examined by measuring glycaemia and dyslipidemia-associated events. TS effectively prevented HF diet-induced increases in the levels of blood glucose, triglyceride, insulin, leptin, and free fatty acid (FFA) and weights of visceral fa; moreover, adipocytes in the visceral depots showed a reduction in size. TS treatment significantly increased the protein contents of glucose transporter 4 (GLUT4) in skeletal muscle; TS also significantly enhanced Akt phosphorylation in liver, whereas it reduced the expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Moreover, TS enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) both in skeletal muscle and liver tissue. Therefore, it is possible that the activation of AMPK by TS resulted in enhanced glucose uptake in skeletal muscle, contrasting with diminished gluconeogenesis in liver. TS exhibits hypolipidemic effect by decreasing the expressions of fatty acid synthase (FAS). Thus, antidiabetic properties of TS occurred as a result of decreased hepatic glucose production by PEPCK and G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic state by TS in HF-fed mice occurred by regulation of GLUT4, G6Pase, and FAS and phosphorylation of AMPK.

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