ABSTRACT
Sirtuin 1 (SIRT1) is one member of the silent information regulator 2 (Sir2)-like family of proteins involved in glucose homeostasis in mammals. It has been reported that SIRT1 modulates endocrine signaling of glucose and fat homeostasis by regulating transcription factors such as forkhead transcription factor 3a (FOXO3a), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator (PGC-1α). However, it is still not clear how SIRT1 is involved in the development of insulin resistance. To determine the location and expression of SIRT1 and its target proteins in rats and analyze the interactions and functions of these proteins in insulin resistance. Forty-eight male Sprague-Dawley rats were randomly divided into four regimen groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr). Animals were fed for 12 weeks and blood samples collected from tail veins at weeks 2, 4, 6, 8 and 12 after fasting for 16 h. Baseline metabolic parameters such as fasting blood sugar, insulin, cholesterol and triglycerides were analyzed. A glucose tolerance test was carried out at the end of the study. Visceral fat, consisting of epididymis and perirenal fat, was isolated and weighed. The pancreas from each animal was also immediately removed. Immunohistochemical staining was performed to detect the locations of SIRT1, FOXO3a, GLUT4, PPARγ and PGC-1α in the ß-cell of the rat pancreas. Expression in the pancreas was analyzed by western blotting. Blood biochemical analysis indicated that the HFa and HFr groups were insulin-resistant. Immunohistochemical staining showed that GLUT4 was a nuclear protein. SIRT1, FOXO3a, PPARγ and PGC-1α were present in both the nucleus and the cytoplasm of ß-cells of pancreatic islets. The expression of SIRT1, GLUT4 and PGC-1α increased significantly in response to CR, but decreased in the HFr and HFa groups. FOXO3a was similar in the CR and the NC groups, whereas it declined in the HFa and HFr groups. PPARγ was elevated in the HFa group, but dropped in the CR and HFr groups. These data suggest that SIRT1 and its regulators are involved in the development of insulin resistance.
Subject(s)
Forkhead Transcription Factors/metabolism , Glucose Transporter Type 4/metabolism , Insulin Resistance/genetics , PPAR gamma/metabolism , RNA-Binding Proteins/metabolism , Sirtuin 1/metabolism , Transcription Factors/metabolism , Animals , Caloric Restriction , Diet, High-Fat , Forkhead Box Protein O3 , Fructose/administration & dosage , Gene Expression Regulation/drug effects , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/ultrastructure , Male , Pancreas/cytology , Pancreas/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Protein Binding , Rats , Rats, Sprague-DawleyABSTRACT
A higher expression of S-100 in tissue of thyroid papillary carcinoma (TPC) vs. thyroid follicular adenoma (TFA) (p < .001) was observed as well as a higher expression of CD83 in the peri-cancerous tissues vs. TFA (p < .001), oppositely, CD83 was negative in the cancerous net. TPC showed greater decreases in levels of CD80 and CD86 than did the TFA. These findings suggest that impaired immune function, absence of CD83-positive mature and activated dendritic cells in cancer nodules may have a role in the pathogenesis of TPC. The low expression of CD80 and CD86 in TPC may help them evade the immune system.
Subject(s)
Adenoma/immunology , Antigens, CD/metabolism , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Dendritic Cells/immunology , Immunoglobulins/metabolism , Membrane Glycoproteins/metabolism , S100 Proteins/metabolism , Adult , Aged , Carcinoma , Carcinoma, Papillary , Case-Control Studies , Cells, Cultured , Female , Humans , Immunohistochemistry , Middle Aged , Thyroid Cancer, Papillary , Thyroid Neoplasms/immunology , Time Factors , Tumor Escape , CD83 AntigenABSTRACT
The aim was to investigate the prevalence of Herpes simplex virus (HSV)-2 infection among pregnant women in southern China and analyze the relationship between the HSV-2 infection and pregnancy outcome. We examined 1740 sera collected from pregnant women aged 21-39 years, using enzyme-linked immunosorbent assay for the detection of specific antibodies against HSV-2. The overall prevalence of HSV-2 infection was 23.56% (95% confidence interval [CI]=21.53-26.00). The prevalence of HSV-2 infection in the women with abnormal pregnancy was 35.93% (95% CI=26.23-42.44) (83/231), which was much higher than that in women who had been pregnant before but without abnormal pregnancy and that in the primipara group. (P<0.05). The presence of HSV-2 antibodies was also associated with status of education. The prevalence of HSV-2 infection in the 26-30-year age group (27.49%) (95% CI=24.53-30.33) was the highest among all age groups. The prevalence of HSV-2 infection in pregnant women in southern China is quite high. Women with asymptomatic or subclinical genital infection should be identified by examining the HSV-2 antibody, which would be helpful to reduce the abnormal pregnancy outcome.
Subject(s)
Herpes Genitalis/epidemiology , Herpesvirus 2, Human/isolation & purification , Mass Screening , Pregnancy Complications, Infectious/epidemiology , Adult , Antibodies, Viral/blood , China/epidemiology , Educational Status , Enzyme-Linked Immunosorbent Assay , Female , Herpes Genitalis/diagnosis , Herpesvirus 2, Human/immunology , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome , Prevalence , Seroepidemiologic Studies , Young AdultABSTRACT
The sirtuin proteins are nicotinamide adenine dinucleotide dependent deacetylases and adenosine diphosphate (ADP)-ribosyl transferases associated with metabolic balance and lifespan extension. Sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4) have been reported to regulate insulin secretion, but their association with the development of insulin resistance and nonalcoholic fatty liver disease remain undefined. The aim of this study was to determine the expression of SIRT1 and SIRT4 in the liver and pancreas of rats fed with different diets and analyze the association of these proteins with insulin resistance and nonalcoholic fatty liver disease. Male Sprague-Dawley rats were randomly divided into the following 4 diet treatment groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr), and these groups were maintained for 12 weeks. Blood biochemical analysis and histopathology indicated that HFa and HFr groups were insulin resistant and developed nonalcoholic fatty livers. SIRT1 was present in the nucleus and cytoplasm of the pancreatic beta-cells, while SIRT4 was located in the cytoplasm. Treatment with the CR diet increased the expression of SIRT1 in both the pancreas and liver, while treatment with the HFa and HFr diets caused a decrease. SIRT4 was upregulated in the liver of rats treated with the HFa diet, but did not change with the CR diet treatment. These data suggest that SIRT1 and SIRT4 were both involved in the development of insulin resistance and nonalcoholic fatty liver disease.