scholarly journals Chromium (D-phenylalanine)3 Supplementation Alters Glucose Disposal, Insulin Signaling, and Glucose Transporter-4 Membrane Translocation in Insulin-Resistant Mice

2008 ◽  
Vol 138 (10) ◽  
pp. 1846-1851 ◽  
Author(s):  
Feng Dong ◽  
Machender Reddy Kandadi ◽  
Jun Ren ◽  
Nair Sreejayan
Keyword(s):  
Insulin Signaling ◽  
Glucose Transporter ◽  
Glucose Disposal ◽  
Glucose Transporter 4 ◽  
Membrane Translocation ◽  
Insulin Resistant

Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure

2007 ◽  
Vol 292 (5) ◽  
pp. R1926-R1933 ◽  
Author(s):  
Xing-Hai Yao ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Adult Female ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Female Offspring ◽  
Female Rat ◽  
Glucose Transporter 4 ◽  
Insulin Resistant ◽  
Rat Offspring

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg−1·day−1 by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCζ. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCζ in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCζ phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.

scholarly journals DHHC7 Palmitoylates Glucose Transporter 4 (Glut4) and Regulates Glut4 Membrane Translocation

2017 ◽  
Vol 292 (7) ◽  
pp. 2979-2991 ◽  
Author(s):  
Keyong Du ◽  
Shoko Murakami ◽  
Yingmin Sun ◽  
Casey L. Kilpatrick ◽  
Bernhard Luscher
Keyword(s):  
Glucose Transporter ◽  
Glucose Transporter 4 ◽  
Membrane Translocation

Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure

2011 ◽  
Vol 300 (5) ◽  
pp. H1637-H1644 ◽  
Author(s):  
Yukihiro Ohta ◽  
Shintaro Kinugawa ◽  
Shouji Matsushima ◽  
Taisuke Ono ◽  
Mochamad A. Sobirin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Serine Phosphorylation ◽  
Glucose Transporter 4

Insulin resistance has been shown to occur as a consequence of heart failure. However, its exact mechanisms in this setting remain unknown. We have previously reported that oxidative stress is enhanced in the skeletal muscle from mice with heart failure after myocardial infarction (MI) ( 30 ). This study is aimed to investigate whether insulin resistance in postinfarct heart failure is due to the impairment of insulin signaling in the skeletal muscle caused by oxidative stress. Mice were divided into four groups: sham operated (sham); sham treated with apocynin, an inhibitor of NAD(P)H oxidase activation (10 mmol/l in drinking water); MI; and MI treated with apocynin. After 4 wk, intraperitoneal insulin tolerance tests were performed, and skeletal muscle samples were obtained for insulin signaling measurements. MI mice showed left ventricular dilation and dysfunction by echocardiography and increased left ventricular end-diastolic pressure and lung weight. The decrease in glucose level after insulin load significantly attenuated in MI compared with sham. Insulin-stimulated serine phosphorylation of Akt and glucose transporter-4 translocation were decreased in MI mice by 61 and 23%, respectively. Apocynin ameliorated the increase in oxidative stress and NAD(P)H oxidase activities measured by the lucigenin assay in the skeletal muscle after MI. It also improved insulin resistance and inhibited the decrease of Akt phosphorylation and glucose transporter-4 translocation. Insulin resistance was induced by the direct impairment of insulin signaling in the skeletal muscle from postinfarct heart failure, which was associated with the enhanced oxidative stress via NAD(P)H oxidase.

scholarly journals Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance

2010 ◽  
Vol 298 (3) ◽  
pp. E565-E576 ◽  
Author(s):  
Jiarong Liu ◽  
Xuxia Wu ◽  
John L. Franklin ◽  
Joseph L. Messina ◽  
Helliner S. Hill ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Glucose Deprivation ◽  
Muscle Cells ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Protein Levels

Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver. Currently, we examined a role for TRIB3 in skeletal muscle insulin resistance. Ten insulin-sensitive, ten insulin-resistant, and ten untreated type 2 diabetic (T2DM) patients were metabolically characterized by hyperinsulinemic euglycemic glucose clamps, and biopsies of vastus lateralis were obtained. Skeletal muscle samples were also collected from rodent models including streptozotocin (STZ)-induced diabetic rats, db/db mice, and Zucker fatty rats. Finally, L6 muscle cells were used to examine regulation of TRIB3 by glucose, and stable cell lines hyperexpressing TRIB3 were generated to identify mechanisms underlying TRIB3-induced insulin resistance. We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells. These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes. TRIB3 acts as a nutrient sensor and could mediate the component of insulin resistance attributable to hyperglycemia (i.e., glucose toxicity) in diabetes.

scholarly journals Insulin Signaling Attenuates GLUT4 Endocytosis in Muscle Cells via GSK3α-Dyn2-Bin1 Interplay

2021 ◽  
Author(s):  
Jessica Laiman ◽  
Julie Loh ◽  
Wei-Chun Tang ◽  
Mei-Chun Chuang ◽  
Bi-Chang Chen ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Postprandial Glucose ◽  
Muscle Physiology ◽  
Centronuclear Myopathy ◽  
Glucose Transporter 4 ◽  
Membrane Fission ◽  
Dynamin 2

AbstractInsulin-induced translocation of glucose transporter 4 (GLUT4) to the plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 into cells is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2), pivotal GTPase catalyzing GLUT4 internalization, is regulated by insulin signaling in muscle cells. The membrane fission activity of Dyn2 is inhibited in muscle cells through binding with the SH3 domain-containing protein Bin1. Phosphorylation of Serine848 on Dyn2 by GSK3α or the mutations of Bin1-SH3 in patients with centronuclear myopathy, elevate the activity of Dyn2 due to reduced binding affinity toward Bin1. The augmented Dyn2 fission activity in muscle cells leads to GLUT4 internalization and Bin1-tubule vesiculation. Together, our findings reveal a new role of insulin signaling in glucose metabolism and muscle physiology via attenuating Dyn2 activity thus regulating GLUT4 endocytosis in muscle cell.

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