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.

MicroRNA-17 impairs glucose metabolism in insulin-resistant skeletal muscle via repressing glucose transporter 4 expression

2018 ◽  
Vol 838 ◽  
pp. 170-176 ◽  
Author(s):  
Dan Xiao ◽  
Tong Zhou ◽  
Yujie Fu ◽  
Rui Wang ◽  
Haiying Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Glucose Transporter 4 ◽  
Insulin Resistant

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.

Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring

2005 ◽  
Vol 288 (2) ◽  
pp. R368-R373 ◽  
Author(s):  
D. S. Fernandez-Twinn ◽  
A. Wayman ◽  
S. Ekizoglou ◽  
M. S. Martin ◽  
C. N. Hales ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Plasma Insulin ◽  
Female Offspring ◽  
Protein Restriction ◽  
Female Rat ◽  
Pregnancy And Lactation

Human adult diseases such as cardiovascular disease, hypertension, and type 2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low-protein (LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin-signaling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine whether female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet, respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 mo of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the two groups; however, LP fasting insulin was approximately twofold that of controls ( P < 0.02). Glucose tolerance during IVGTT was comparable between the two groups; however, LP peak plasma insulin at 4 min was approximately threefold higher than in controls ( P < 0.001). LP plasma insulin area under the curve was 1.9-fold higher than controls ( P < 0.02). In Western blots, both muscle protein kinase C-ζ expression and p110β-associated p85α in abdominal fat were reduced ( P < 0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin-signaling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and, hence, an increased risk of type 2 diabetes.

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