To investigate the possibility of using C-peptide to replace insulin in homeostasis model assessment (Homa) to evaluate insulin resistance and islet beta cell function. Oral glucose tolerance test (OGTT) was performed in 21 normal subjects, whose venous blood was drawn before taking glucose and 30, 60, 120 minutes after taking glucose. Insulin and C-peptide were determined with radioimmune assay. Homa indices of insulin resistance and islet beta cell function were calculated. Multiple stepwise linear regression model of insulin resistance was measured using C-peptide x blood glucose as independent variables and Homa-IR was used as the dependent variable, while the model of islet beta cell function was determined using C-peptide/(fasting blood glucose - 3.5) as the independent variable and Homaislet as the dependent variable. The modified Homa formula were: Homa-IR (CP) = 1.5 + fasting blood glucose x fasting C-peptide/2800 (F = 5. 511, P = 0.029), Homa-islet (CP-Normal) = 0.27 x fasting C-peptide /(fasting blood glucose - 3.5) + 50, and Homa-islet (CP-DM) = 0.27 x fasting C-Peptide/(fasting blood glucose - 3.5) (F = 212.961, P = 0.000), respectively. The modified Homa-IR (CP) and Homa-IR, Homa-islet (CP) and Homa-islet were highly correlated (r =0.689 and r = 0.788; all P = 0.000). Using Homa and modified Homa formula to evaluate the insulin resistance and islet beta cell function both in the normal and diabetic subjects was similar. Fasting C-peptide can substitute insulin in Homa model to assess insulin resistance and islet beta cell function. The modified homeostasis model assessment may be applied in the diabetics using exogenous insulin.
To explore the curative effects of 1-(3-fluorophenyl)-5-methyl-2- (1H)-pyridone (FMP) on renal fibrosis in rats. The effects of FMP on the cell proliferation and Fn secretion were measured by methyl thiazolyl tetrazolium and enzyme-linked immunoabsorbent assay, respectively. FMP obviously inhibited the proliferation and Fn secretion in rat renal fibroblast 48 hours after the treatment. FMP (1 000 microg/ml) obviously inhibited the proliferation of rat renal fibroblast 24 hours after the treatment. 1-(3-Fluorophenyl) -5-methyl-2-(1H)-pyridone can obviously inhibit the proliferation of rat renal fibroblast, which may be effective for renal interstitial fibrosis prevention and treatment.
To determine the changes in serum and urine ceruloplasmin (Cp) concentrations in type 2 diabetes, and to explore its clinical significance. Cp concentrations of 57 serum samples were measured by radioimmunoassay and ratenephelometry. In the meantime, the serum and urine Cp concentrations in 110 healthy individuals and 104 type 2 diabetic patients were determined by ratenephelometry. For analysis and comparison, 104 type 2 diabetic patients were divided into imperfect glycemic control subgroup (n = 54) and perfect glycemic control subgroup (n = 50), diabetic nephropathy subgroup (n = 47) and non-diabetic nephropathy subgroup (n = 57). Serum Cp concentrations obtained with the radioimmunoassay and ratenephelometry methods were highly correlated and essentially indistinguishable. The cut-off point of the serum Cp concentrations was 542 mg/L and that of the ratio of Cp and creatinine was 0. 892 ng/mmol, which was determined according to the upper limit of 97.5% credit intervals or 97.5% percentile in 110 healthy individuals. Cp concentrations in type 2 diabetic patients were significantly higher than those in the healthy individuals (P <0.001). Of the type 2 diabetic patients, the imperfect glycemic subgroup had higher serum Cp concentrations than those of the perfect glycemic subgroup (P <0.01). The urine ratio of Cp and creatinine in diabetic nephropathy subgroup was significantly higher than that in non-diabetic nephropathy subgroup (P < 0.001). Urine ratio of Cp and creatinine in diagnosing diabetic nephropathy had 91.4% of sensitivity, 61.4% of specificity, and 75.0% of concordance. Detection of serum Cp levels has some reference value in understanding the state of diabetes. Combined determination of urine ratio of Cp and creatinine and ratio of albumin and creatinine is significant in the early diagnosis of diabetic nephropathy.
To investigate the effect of the expression of pituitary tumor transforming gene (PTTG), endostatin and basic fibroblast growth factor (bFGF) in invasive pituitary adenomas. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of PTTG, endostatin, and bFGF mRNA in invasive and non-invasive pituitary adenomas. The expression of PTTG and bFGF significantly increased in the invasive pituitary adenomas (all P < 0.01) compared with those in the non-invasive pituitary adenomas. However, the expression of endostatin significantly decreased in the invasive pituitary adenomas compared with the non-invasive pituitary adenomas (P < 0.01). Increased expression of human PTTG and bFGF, and decreased expression of endostatin may be related to the genesis of tumor invasiveness. The feasible mechanism may be related to that the increased expression of PTTG plays a role in pituitary tumor invasiveness by altering the balance of tumor angiogenesis.
To prospectively investigate the relationship between high-sensitive C-reactive protein (hs-CRP) and Type 2 diabetic nephropathy. We assayed serum hs-CRP concentration in 55 normal controls, 66 Type 2 diabetic patients without diabetic nephropathy (DN) and 68 Type 2 diabetic patients with DN by ELISA. A 5-year prospective study was designed to investigate the changes of urinary albumin excretion (UAE), serum hs-CRP concentration, and kidney funciton in targeted intervention including blood glucose and blood pressure in 58 diabetic patients without DN at the baseline. Baseline hs-CRP concentration was the highest in Type 2 diabetic patients with DN, followed by Type 2 diabetic patients without DN, and the lowest in normal controls. After 5-year intervention, hs-CRP concentration at the endline was significantly lower than that at the baseline in the patients in whom DN didn't occur at the endline (P 0.05). Both baseline and endline, the hs-CRP concentrations in the patients in whom DN occured at the endline were significantly higher than those without DN at the endline. Higher serum hs-CRP concentration in patients with Type 2 diabetes may be a risk factor that gives rise to DN. To some extent hs-CRP can predict the occurrence of DN in Type 2 diabetic patients.
To evaluate the protective effect of ambroxol on acute hydrochloric acid-induced lung injury in rats. Thirty pathogen-free SD rats were randomly divided into 3 groups: Group A (n=10) served as control group, and received intracheal instillation of normal saline (NS, pH5.3, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; Group B (n=10) received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; and Group C received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal ambroxol (50 mg/kg/d, 3 days). Five hours after the instillation of the injury vehicle, the arterial gas was examined, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) in the blood and homogenate of harvested lung were assayed respectively. PaO2 in Group B was significantly lower than that in Group A and C (P 0.05). MDA in the lungs of Group B increased obviously, and levels of SOD in the lung and blood decreased significantly in Group B (Group B vs Group A, P 0.05). Ambroxol can inhibit lipid peroxidation and increase antioxidant activity, which may be one of the mechanisms in protecting lung tissue from hydrochloric acid-induced injury.
To observe the cleavage of nucleolin (C23) during apoptosis induced by oxidative stress and to clarify the effect of heat shock response (HSR) on the cleavage of nucleolin and its possible molecular mechanism. We added 0.5 mmol/L peroxide hydrogen (H2O2 ) into cultured cells to mimic oxidative stress. Apoptosis and cleavage of C23 were detected using caspase-3 colorimetric assay and Western blotting respectively. HSR was performed to observe the effect of HSR on cleavage of C23 induced by oxidative stress, and over-expressions of HSP70 and HSP25 were detected by Western blotting. Activity of caspase-3 increased significantly after 2 hours of 0.5 mmol/L H2O2 treatment, and reached the peak after 12 hours. The cleavage of C23 appeared 30 minutes to 1 hour after the treatment of H2O2 as indicated by a cleaved fragmentation of 80 kD, which was significantly inhibited by HSR. Moreover, HSR could induce HSP70 and HSP25 over-expressions. Oxidative stress can induce the activation of caspase-3, cleavage of C23, and apoptosis. HSR can significantly inhibit the cleavage of C23 induced by oxidative stress, which is related to the over-expressions of HSP70, HSP25, and other stress proteins.
To investigate the reversal effect of multidrug resistance (MDR) mediated by glutathione (GSH) detoxifcation system in K562/A02 cell line by neferine and erythromycin. Cellular GSH concentration was examined by biochemical analyses with DTNB. Cellular GSH concentration in K562/A02 cell line [(137.34 +/- 33.10) mg/mgprot] was higher than that in K562 cell line [(73.38+/-10.02) mg/mgprot] (P < 0.05), and 1.87-fold greater in K562/A02 cell line compared with that in K562 cell line. Cellular GSH concentration in K562/A02 cell line treated with Nef10 mg/L, EM100 mg/L, Nef10 mg/L + EM100 mg/L, and VRP5 mg/L for 2 days [(69.01 +/- 15.99) mg/mgprot, (70.57 +/- 11.93) mg/mgprot, (65.74 +/- 13.37) mg/mgprot, and (70.86 +/- 16.16) mg/mgprot, respectively] decreased than that in K562/A02 cell line without drugs (P < 0. 05). Increase of cellular GSH concentration was one of the MDR mechanisms in K562/A02 cell line. Decrease of cellular GSH concentration may be one of the MDR reversal mechanisms in K562/A02 cell line by neferine and erythromycin.