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Background Lipid metabolism imbalance is tightly linked to the development and progression of multiple diseases. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is important for the regulation of lipid metabolism. However, whether silicosis is associated with lipid metabolic abnormalities has yet to be explored. Objective To observe the changes of lipid deposition, cholesterol, and phosphorylated proteins of PI3K/AKT/mTOR pathway in silicon dioxide (SiO2)-induced MLE-12 cells and to explore potential mechanism of lipid composition regulated though the pathway. Methods (1) MLE-12 cells were stimulated with 50 mg·L−1 SiO2 suspension, and divided into fourgroups: a control group and three SiO2 groups (12, 24, and 48 h of stimulation). (2) Cellproliferation was detected to determine an optimal dose of LY294002, an inhibitor of PI3K protein. LY294002 at 5 μmol·L−1 was used for further study, in which MLE-12 cells cultured for 48 h were divided into four groups: a control group; a 50 mg·L−1 SiO2 suspension stimulation group; a 50 mg·L−1 SiO2 suspension and 5 μmol·L−1 LY294002 treatment group; a 5 μmol·L−1 LY294002 treatment group. Total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE; total cholesterol minus free cholesterol), and triglycerides (TG) were measured with enzyme assay kits. Lipid deposition was observed using Oil Red O staining. The expressions of p-PI3K, p-AKT, and p-mTOR proteins were detected by Western blotting. Results (1) The contents of TC, FC, and CE in the 50 mg·L−1 SiO2-induced MLE-12 cells were increased compared to those of the control group in a time-dependent manner by trend analysis, and the increment at 24 and 48 h were significant. By 48 h, the contents of cholesterol indicators were all elevated: TC from (2.242±0.181) mg·g−1 to (5.148±0.544) mg·g−1, FC from (1.923±0.158) mg·g−1 to (4.168±0.433) mg·g−1, and CE from (0.318±0.067) mg·g−1 to (0.978±0.134) mg·g−1, compared with the control group (P<0.01). The changes of TG were not significant (P>0.05). The SiO2 suspension induced orange-red particle deposition in the MLE-12 cells, especially at 48 h (P<0.01). The protein expression levels of p-PI3K, p-AKT, and p-mTOR in SiO2-stimulated MLE-12 cells were higher than those of the control groups with the prolongation of stimulation time, which peaked at 48 h (P<0.01). (2) The contents of TC, FC, and CE in MLE-12 cells of the SiO2 + LY294002 group were decreased, comparing to those of the SiO2 stimulation only group (P<0.01), companied with less orange-red lipid deposition, and suppressed protein expression levels of p-PI3K, p-AKT, and p-mTOR (P<0.01). Conclusion SiO2 could induce increases of cholesterol and lipid deposition through activation of PI3K/AKT/mTOR signaling pathway in MLE-12 cells.
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Objective To understand the effect of astragalus on insulin resistance and plasma amylin levels in newly diagnosed type 2 diabetic patients.Methods 88 patients of newly diagnosed type 2 diabetes were randomly divided into three groups:Group A (lifestyle intervention group) contained 30 patients,Group B (metformin treatment group) also contained 30 Patients,and Group C (astragalus and metformin treatment group) contained 28 Patients.Patients in group A were intervened with the control of diet,blood pressure and lipids level; patients in group B were additionally treated with metformin on the basis of group A; patients in group C were additionally treated with metformin and astragalus on the basis of group A.The course for both treatments were 8 weeks.Various clinical and biochemical parameters were detected before and after the treatment in all three groups and enzyme-linked immunosorbent assay was adopted for the detection of plasma amylin.Results Fasting blood glucose levels were significantly decreased after treataent in the three groups (t=-2.696、-4.029、-3.995,P＜0.05) ; insulin resistance index reduced in group B and group C (t=-2.599、-3.813,P＜0.05),the difference between group C and group B was statistically significant (t=-2.334,P＜0.05) ;treatments of group B and group C could improve the beta cell function index (t=2.303、2.384,P＜0.05),and they also could increase the plasma amylin level (t=2.341、3.045,P＜0.05).Conclusion Astragalus and metformin can improve insulin resistance index and increase plasma amylin levels in newly diagnosed type 2 diabetic patients.
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Objective To understand the serum levels of advanced glycation end products (AGEs),soluble receptor for advanced glycation end products (sRAGE) in newly diagnosed patients with type 2 diabetes.Methods 60 patients of newly diagnosed type 2 diabetes were chosen from 2010 September to 2011 December in Department of Endocrinology Changshou Chinese medicine hospital in Jiangsu Province,and 30 healthy people were screened as control group.Various clinical and biochemical parameters were detected,using enzyme-linked immunosorbent assay for the detection of serum AGEs and sRAGE levels.Results The levels of serum AGEs in newly diagnosed type 2 diabetic patients and control group were (1379.2 ± 431.8) and (1154.5 ±326.4) pg/ml,and there were significant differences between two groups (P＜0.05).The levels of serum sRAGE in newly diagnosed type 2 diabetic patients and control group were (14.6± 9.3)and (19.5 ± 8.9)ng/ml,and there were also significant differences between two groups (P＜0.05).The level of serum AGEs in newly diagnosed type 2 diabetic patients was positive correlation with glycosylated hemoglobin (HbA1c),and the level of serum sRAGE was associated with low density lipoprotein cholesterol (LDL-C) negative correlation.Conclusion The level of serum AGEs increase in newly diagnosed type 2 diabetic patients,and the level of serum sRAGE decrease in newly diagnosed type 2 diabetic patients.
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Objective To understand the effect of astragalus on serum levels of advanced glycation end products (AGEs),soluble receptor for advanced glycation end products (sRAGE) in newly diagnosed patients with type 2 diabetes.Methods 60 patients of newly diagnosed type 2 diabetes were randomly divided into control group (28 patients) and treatment group (28 patients),the control group was given control of blood glucose,blood pressure,lipids and other necessary treatment,and the treatment group was additionally treated with astmgalus granule based on the control group.The course for both treatments is 12 weeks.Various clinical and biochemical parameters were tested before and after treatment in both groups with enzyme-linked immunosorbent assay for the detection of serum AGEs,sRAGE levels.Results ① Glycosylated hemoglobin (HbA1c) in the control group after treatment (7.28± 0.83)％ was significantly decreased than before treatment (9.57±1.14) ％,the difference was statistically significant (t＝5.75,P＜0.05); glycerin three greases (TG) in the control group after the treatment (1.45± 0.39)mmol/L decreased significantly compared with those before treatment (1.92± 1.01)mmol/L,the difference was statistically significant(t＝2.79,P＜0.05); ② HbA1c (7.16± 0.88) ％ in the treatment group after treatment was significantly decreased than before treatment (9.29± 1.62)％,the difference was statistically significant (t＝6.08,P＜0.05) ; TG (1.53 ± 0.41) mmol/L in the treatment group after treatment was significantly decreased compared with those before treatment (2.11 ± 0.79)mmol/L,the difference was statistically significant (t ＝ 2.40,P ＜ 0.05) ; the levels of serum sRAGE (20.38 ± 8.01) ng/ml in the treatment group after treatment increased obviously compared with those before treatment (15.10 ± 9.22)ng/ml,the difference was statistically significant (t＝-2.29,P＜0.05); ③ The level of serum sRAGE (20.38 ± 8.01) ng/ml in the treatment group after treatment increased obviously than the levels of serum sRAGE (15.13 ± 9.27)ng/ml in the control group after treatment,the difference was statistically significant (t＝-1.17,P＜0.05).Conclusion Astragali can increase serum sRAGE expression in newly diagnosed type 2 diabetic patients.
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Objective To evaluate desmopressin stimulated inferior petrosal sinus sampling in diagnosing Cushing′s disease.Methods Sixteen ACTH-dependent Cushing′s disease patients underwent bilateral desmopressin stimulated inferior petrosal sinus ( IPS ) sampling because of negative or equivocal magnetic resonance imaging.Cortisol response to high-dose dexamethasone suppression test was also evaluated.ACTH sampling was taken from a peripheral vein and bilateral IPS before and both 5 and 10 min after injection of desmopressin.Diagnosis was based on the ratio of ACTH level in between IPS to peripheral vein by desmopressin test.Diagnosis was confirmed after surgery.Results High-dose dexamethasone suppression test showed suppressible in 9 of 16 patients with Cushing′s disease.An IPS gradient ＞2 was found in 14 of the 16 cases (87.5％ )with Cushing′s disease after desmopressin injection,while before injection the respective figure was 12 of 16 (75.0％).No severe adverse effects were observed during or after the procedure.Conclusion Desmopressin test during bilateral IPS sampling is a safe and effective diagnostic procedure in Cushing′s disease.