Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high­fat­diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3­kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate­1 (IRS­1), glucose transporter type 4 (GLUT­4), nuclear factor (NF)­κB and tumor necrosis factor (TNF)­α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high­fat­diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high­dose testosterone treatment. Low­dose testosterone induced upregulation in the levels of IRS­1, AKT, GLUT­4 protein, NF­κB, TNF­α and PI3K, compared with those in the animals fed a high­fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS­1, AKT, GLUT­4, NF­κB, TNF­α and PI3K. Compared with the rats in the high­fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS­1, AKT and GLUT­4, and downregulation of the mRNA levels of NF­κB, TNF­α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS­1, AKT and GLUT­4, and marked increases in the mRNA levels of NF­κB, TNF­α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low­dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.

Association of plasma glucose, insulin, and cardiovascular risk factors in overweight and obese children.

OBJECTIVE: To investigate the association between fasting plasma glucose (FPG), 2-hour post challenge plasma glucose (2hPG), fasting plasma insulin (FINS), 2-hour post challenge plasma insulin (2hINS), and cardiovascular risk factors in obese and overweight children. METHODS: This is a cross-sectional study of 452 obese and overweight children (male: 312, female: 140, aged 6-16 years). This study was conducted in the Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin, China between June 2008 and November 2012. Anthropometries and blood analysis were carried out. Pearson correlation analysis and multiple stepwise linear regression analysis were used to investigate the association among FPG, 2hPG, FINS, 2hINS and cardiovascular risk factors. RESULTS: Body mass index, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure, and triglyceride were highly correlated with FINS. Fasting plasma insulin influenced greater variance in most cardiovascular risk factors than 2hPG and 2hINS. CONCLUSION: Fasting plasma insulin was closely associated with most cardiovascular risk factors compared with FPG, 2hPG and 2hINS.

[Correlation between vaspin concentration and insulin sensitivity in the visceral adipose tissue of young obese rats].

OBJECTIVE: To investigate the correlation between visceral adipose tissue-derived serine protease inhibitor (vaspin) concentration and insulin sensitivity in the visceral adipose tissue of young obese Sprague-Dawley (SD) rats. METHODS: Twenty-four SD rats which had been weaned 3 weeks before were randomly divided into two groups (n=12 each) to receive a high-fat and normal diet. The weight and abdominal circumference (AC) of each rat were measured, the fasting plasma glucose (FPG) and fasting insulin (FINS) in blood from the angular vein were measured after 12 hours of fasting and blood glucose (BG) and insulin (INS) levels in blood from the angular vein were measured at 60 and 120 minutes after intraperitoneal injection of 50% glucose (2 g/kg). The rats were sacrificed, and their liver and visceral adipose tissue were weighed. The vaspin concentration of the visceral adipose tissue in each rat was measured using ELISA. Correlation analysis was performed on the vaspin concentration and other indices. RESULTS: Compared with the normal diet group, the high-fat diet group showed significantly higher weight, AC, weight of visceral adipose tissue, FPG, FINS, 120 minute INS level, vaspin concentration, homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of ß cell function (HOMA-ß) (P<0.05) Insulin sensitivity index (ISI) was significantly lower (P<0.01). Vaspin concentration was positively correlated with visceral adipose tissue and liver weight, AC, 120 minute INS level, FPG, FINS, HOMA-IR and HOMA-ß (P<0.05), and negatively correlated with ISI (P<0.05). CONCLUSIONS: High expression of vaspin is associated with insulin resistance in young obese SD rats. Vaspin is presumably an adipocytokine that can increase insulin sensitivity, promote insulin secretion by islet ß-cells and improve glucose tolerance, and it may be involved in insulin resistance and the disturbance of carbohydrate metabolism.

Experimental study on monitoring gene expression by noninvasive method in rabbit VX2 liver tumor model / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of monitoring therapeutic effect of adenovirus vector containing IL12-IRES-CKb gene on a rabbit VX2 liver tumor model by using phosphorous-31 magnetic resonance spectroscopy (31P MRS).</p><p><b>METHODS</b>A total of 18 healthy New Zealand White rabbits were used to generate animal models by implanting VX2 tumor chips into livers through laparotomy. Tumor-bearing animals were randomly divided into three groups and were injected with AdCMVIL12-IRES-CKb, AdCMV-Empty and saline respectively via ear veins. 31P MRS scan was performed after animals were fed with creatine solution for five days. Animals were euthanized thereafter and tumors were removed for pathological examination, immunohistochemistry (IHC) staining and protein analysis (Western blot).</p><p><b>RESULTS</b>The intrahepatic and seral expressions of creatine kinase (CKb) and IL-12 were detected only in AdCMVIL12-IRES-CKb group. Tumor diameters pre- and post- treatment in three groups were 1.63+/-0.04 vs 1.62+/-0.03 in AdCMVIL12-IRES-CKb group (P = 0.229), 1.59+/-0.05 vs 1.84+/-0.11 in AdCMV-Empty group (P = 0.003) and 1.60+/-0.02 vs 2.07+/-0.12 in saline group (P = 0.001), respectively. Pcr Changes between pre- and post- treatment among the three groups were compared (F = 6.235, P value is less than 0.05). PCr increased significantly in AdCMVIL12-IRES-CKb group as compared to AdCMV-Empty (P = 0.004) and saline group (P = 0.049), whereas no change found between AdCMV-Empty and saline group (P = 0.153).</p><p><b>CONCLUSION</b>31P MRS, an effective and non-invasive functional imaging method, can be used to monitor the therapeutic effect of adenovirus vector containing IL12-IRES-CKb gene on rabbit VX2 liver tumor model through detecting metabolic product of imaging reporter gene CKb (pCr).</p>