ABSTRACT
Background: Testosterone deficiency is reportedly correlated with an elevation of cholesterol in plasma, but the mechanism remains unclear. Our objective was to investigate the effects of testosterone deficiency on cholesterol metabolism and the corresponding molecular changes in vivo and in vitro. Methods: SD rats were randomized into three groups: sham-operated (SHAM), subtotal orchiectomized (SO), and orchiectomized (ORX) and fed for 8 weeks. HepG2 cells were cultured with medium containing testosterone with the final concentrations of 0, 10, 30, and 300 nM. Method of isotope tracing and fluorescence labelling was adopted to investigate cholesterol metabolism. Several key molecules of cholesterol metabolism were also analyzed. Results: SO and ORX rats displayed dysfunctional liver uptake of cholesterol. HepG2 cells incubated with testosterone of lower and excessive level exhibited reduced capacity of cholesterol uptake. Further investigation revealed that lack of testosterone induced increased proprotein convertase subtilisin/kexin type 9 (PCSK9) and decreased low-density lipoprotein receptor (LDLR) both in vivo and in vitro. Moreover, the androgen receptor (AR) antagonist flutamide mimicked the effects of testosterone deficiency on PCSK9 and LDLR indicating the role of AR as a mediator in triggering attenuating liver cholesterol uptake in which testosterone instead of dihydrotestosterone (DHT) is the major functional form of androgen. Conclusion: Testosterone deficiency attenuated cholesterol liver uptake mediated by the PCSK9-LDLR pathway, in which AR and testosterone without transforming to DHT play important roles.
ABSTRACT
Objective@#To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves′ orbitopathy.@*Methods@#Twenty-seven patients with active moderate-to-severe Graves′ orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves′Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody (TRAb), anti-thyroperoxidase antibody (TPOAb), and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+ T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point.@*Results@#TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+ /CD8+ ratio were gradually decreased after treatment. However, change of CD8+ T cells was not significant (P>0.05).@*Conclusion@#High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.
ABSTRACT
Objective To study the effect of high-dose methylprednisolone intravenous pulse therapy on immunoglobulins and CD series in patients with active moderate-to-severe Graves' orbitopathy. Methods Twenty-seven patients with active moderate-to-severe Graves' orbitopathy were enrolled in this study. All the patients received iv methylprednisolone pulse therapy for 12 weeks according to the 2016 European Thyroid Association/European Group on Graves'Orbitopathy(EUGOGO) Guidelines. Serum thyroidal autoantibodies, such as thyroid-stimulating hormone receptor antibody ( TRAb) , anti-thyroperoxidase antibody ( TPOAb) , and serum immunoglobulins, such as IgG, IgE, IgA, IgM were evaluated at the baseline, at the end of 4th and 12th week. Percentages of CD3+ T cells, CD4+ T cells, CD8+T cells and CD19+ B cells, CD16+ or CD56+ NK cells were also evaluated at each time point. Results TRAb, TPOA and IgE, IgG, IgA were significantly decreased both after 4th week and after 12th week (all P<0.05). Percentages of CD3+ T cells, CD4+ T cells and CD4+/CD8+ ratio were gradually decreased after treatment. However, change of CD8+T cells was not significant (P>0.05). Conclusion High-dose methylprednisolone may exert an immunosuppressive effect not only by modifying humoral and cellular immune functions, but also by decreasing serum immunoglobulins.
ABSTRACT
Objective We aimed to investigate whether sex hormone levels including total testosterone, estradiol, estradiol/total testosterone, and dehydroepiandrosterone ( DHEA ) were associated with macrovascular complications among Shanghai community-dwelling diabetic men. Methods Relying on the Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study (ChiCTR1800017573, www.chictr.org.cn), 2147 male diabetic participants were recruited from 10 communities. Carotid plaques and common carotid artery ( CCA) diameters were detected by carotid ultrasound. Cardiovascular disease ( CVD) was defined as a self-reported diagnosis of CVD, including coronary heart disease, myocardial infarction, or stroke. Results ( 1) The prevalence of CVD in this study was 36. 0％, and patients with CVD had higher rates of hypertension and dyslipidemia than those without CVD. ( 2) After controlling for multiple factors, serum DHEA levels were negatively correlated with the prevalence of CVD while estradiol levels were positively correlated with both the prevalences of CVD and carotid plaque, estradiol/total testosterone ratio was also positively correlated with the prevalence of CVD. ( 3) In subgroup with unilateral/bilateral CCA plaque, and after controlling for multiple factors, total serum testosterone was negatively associated with the mean CCA diameter. Conclusion The incidence of macrovascular complications was lower in male diabetic patients with higher serum total testosterone and DHEA levels and lower estradiol levels, suggesting that sex hormone levels may be a window for the diagnosis and treatment of diabetic macrovascular complications.
ABSTRACT
Objective To assess vitamin D levels in eastern China by a standard measurement. Methods The data were from a 2014 Survey on the Prevalence in East China for Metabolic Diseases and Risk Factors-China data base. There were 12662 subjects included in this cross-sectional study from February 2014 to June 2016. We assessed the vitamin D levels of natural population by a standard classification in which serum 25-hydroxy vitamin D (25-OHD)<50 nmol/ L was defined as vitamin D deficiency. Results The average serum 25-OHD level was (40. 5 ± 12. 5)nmol/ L, and there were 80. 3% subjects who would be classified as vitamin D deficiency; The average serum 25-OHD level of women was significantly lower than that of men (P< 0. 05); The serum 25-OHD concentrations of the <30, 30-39, 40-49, 50-59, 60-69, ≥70 age groups were 37. 81(31. 98-43. 52)nmol/ L, 39. 46(33. 87-45. 72) nmol/ L, 41. 17(34. 10-48. 65) nmol/ L, 40. 67(34. 20-49. 02) nmol/ L, 44. 00 (35. 67-53. 93) nmol/ L, 44. 14 (34. 61-55. 85)nmol/ L for males, and 36. 86 (30. 52-43. 75) nmol/ L, 37. 11 (31. 68-43. 23) nmol/ L, 36. 94 (30. 72-43. 71) nmol/ L, 38. 42(32. 08-46. 41) nmol/ L, 38. 58(31. 04-46. 21) nmol/ L, 37. 31(29. 34-47. 17) nmol/ L for females in corresponding subgroups. Conclusion The prevalence of vitamin D deficiency of natural population in eastern China was common, the levels of vitamin D in women were lower than those of men. However, the vitamin D levels were tended to be increasing with the advance of age.
ABSTRACT
Objective To assess vitamin D levels in eastern China by a standard measurement. Methods The data were from a 2014 Survey on the Prevalence in East China for Metabolic Diseases and Risk Factors-China data base. There were 12662 subjects included in this cross-sectional study from February 2014 to June 2016. We assessed the vitamin D levels of natural population by a standard classification in which serum 25-hydroxy vitamin D (25-OHD)<50 nmol/ L was defined as vitamin D deficiency. Results The average serum 25-OHD level was (40. 5 ± 12. 5)nmol/ L, and there were 80. 3% subjects who would be classified as vitamin D deficiency; The average serum 25-OHD level of women was significantly lower than that of men (P< 0. 05); The serum 25-OHD concentrations of the <30, 30-39, 40-49, 50-59, 60-69, ≥70 age groups were 37. 81(31. 98-43. 52)nmol/ L, 39. 46(33. 87-45. 72) nmol/ L, 41. 17(34. 10-48. 65) nmol/ L, 40. 67(34. 20-49. 02) nmol/ L, 44. 00 (35. 67-53. 93) nmol/ L, 44. 14 (34. 61-55. 85)nmol/ L for males, and 36. 86 (30. 52-43. 75) nmol/ L, 37. 11 (31. 68-43. 23) nmol/ L, 36. 94 (30. 72-43. 71) nmol/ L, 38. 42(32. 08-46. 41) nmol/ L, 38. 58(31. 04-46. 21) nmol/ L, 37. 31(29. 34-47. 17) nmol/ L for females in corresponding subgroups. Conclusion The prevalence of vitamin D deficiency of natural population in eastern China was common, the levels of vitamin D in women were lower than those of men. However, the vitamin D levels were tended to be increasing with the advance of age.
ABSTRACT
<p><b>BACKGROUND</b>Lymphocyte function and homeostasis is associated with immune defence to infection. Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia. The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.</p><p><b>METHODS</b>Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study. Annexin V and propidiumiodide (PI) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry. Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2, cytochrome c (Cyt-C), caspase-9 and caspase-3 were analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P < 0.05). Transmission electron microscopy showed lymphocyte shrinkage and breakage, chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9, caspase-3 and Cyt-C were elevated (P < 0.05) in diabetic patients.</p><p><b>CONCLUSIONS</b>The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population. Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Apoptosis , Physiology , Caspase 3 , Genetics , Caspase 9 , Genetics , Diabetes Mellitus, Type 2 , Metabolism , Lymphocytes , Cell Biology , Metabolism , Microscopy, Electron, Transmission , Mitochondria , Metabolism , Real-Time Polymerase Chain Reaction , bcl-2-Associated X Protein , GeneticsABSTRACT
<p><b>BACKGROUND</b>The glucose fluxes of individuals with prediabetes in Chinese population are not clear. This study was to determine whether the endogenous glucose production (EGP), oral glucose rate of appearance (Ra) and glucose rate of disappearance (Rd) were different in Chinese individuals with prediabetes under fasting conditions and following an oral glucose challenge.</p><p><b>METHODS</b>Five subjects with type 2 diabetes, 5 subjects with prediabetes and 5 non-diabetic subjects matched for age, weight, fat free mass and body mass index underwent a 180 minute stable glucose isotope tracing ([6, 6-(2)H2] glucose, [1-(13)C] glucose, and [U-(13)C] glucose) study under fasting and after ingestion of a 75 g oral glucose load. Isotope glucose enrichment was measured by gas chromatography-mass spectrometry. Insulin sensitivity was estimated using the oral glucose tolerance test (OGTT)-derived insulin sensitivity index, β cell function was determined by the insulinogenic index (δI30/δG30).</p><p><b>RESULTS</b>The insulin sensitivity index (P = 0.043) and insulinogenic index (P = 0.021) were decreased in subjects with prediabetes compared with non-diabetes. Fasting EGP was slightly higher (P = 0.29) and postprandial EGP was comparable in subjects with prediabetes and non-diabetes during 120 minutes after glucose ingestion, but nadir EGP occurred later in prediabetic than non-diabetic subjects. Ra did not differ among the three groups. Rd was substantially lower in subjects with prediabetes than non-diabetes after glucose intake (P = 0.013).</p><p><b>CONCLUSION</b>The mild hyperglycemia observed among individuals with prediabetes may result from decreased Rd during the postprandial state.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Blood Glucose , Metabolism , Case-Control Studies , Diabetes Mellitus, Type 2 , Blood , Fasting , Blood , Glucose , Metabolism , Glucose Tolerance Test , Hyperglycemia , Blood , Isotope Labeling , Prediabetic State , BloodABSTRACT
The fasting and 2 h levels of glucagon, somatostatin ( SS), and C-peptide during 75 g oral glucose tolerance test in 60 patients with type 2 diabetes and 34 normal subjects were determined. Compared with control group, the fasting levels of glucagon and SS and 2 h levels of SS after glucose loading significantly decreased,while the fasting and 2 h levels of C-peptide increased in diabetes group. The 2 h levels of these hormones were significantly higher than the fasting levels in two groups. Compared with control group, the increased folds of glucagon ( 1.40±0.48 vs 1.20±0. 30, P＜0. 05 ) and SS( 2.79±2. 17 vs 1.14±0. 22, P＜0. 01 ) levels after glucose loading were higher and that of C-peptide level ( 3.58 ±3. 10 vs 8. 33 ± 6. 99, P＜0. 01 ) was lower in diabetes group. The levels of fasting glucagon were positively correlated with that of fasting SS in two groups( both P＜0. 01 ). These results suggest that disturbance exists in hormones from α and δ cells besides the dysfunction of β cells in patients with type 2 diabetes.
ABSTRACT
Rat hepatic oval cell model was induced by hyperglycemia and streptozotocin in vivo. Expression of insulin and mRNA expression of pancreatic transcription factors(Nkx6.1, PDX-1) were carried out. It showed that under high glucose, liver tissues were positive for insulin staining, the expression of Nkx6.1 and Pdx-1mRNA was significantly enhanced, and insulin-1mRNA was found to be expressed. The result suggests that under high glucose, hepatic oval cells can differentiate into insulin-producing cells.
ABSTRACT
The response of glueagon to the change of glucose and its relation to blood pressure in 71 eidely patients with type 2 diabetes was investigated. The results showed that the postprandial increment of glucagon in the group of patients with postprandial 2h plasma glucose increment<2.5 mmol/L was significantly higher than that in the group with plasma glucose inerement≥ 2.5 mmoi/L (P<0. 05). The postprandial increment of glucagon in patients with normal blood pressure was significantly higher than that in patients with hypertension (P<0.05). The results suggest that the decreased response of glucagon to the change in plasma glucose in elderly patients with type 2 diabetes is related to increased blood glucose and high blood pressure.
ABSTRACT
ed in vitro and in vivo,which was inhibited by aspirin treatment.
