Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
J Diabetes ; 11(12): 958-970, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31020790

ABSTRACT

BACKGROUND: Brown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear. METHODS: Diabetic mice were induced by streptozotocin (STZ) combined with a high-fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a ß3 -adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24-hour urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress-related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/ß-klotho/FGF receptor 1c and AMP-activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator-activated receptor-γ coactivator-1α [Pgc1α]) were also evaluated. RESULTS: Compared with untreated STZ-diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24-hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 µg/24 h; P < 0.05) and 8-OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney. CONCLUSIONS: Activating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.


Subject(s)
Adipose Tissue, Brown/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/prevention & control , Dioxoles/pharmacology , Hypoglycemic Agents/pharmacology , Kidney/drug effects , AMP-Activated Protein Kinases/metabolism , Adipokines/blood , Adipose Tissue, Brown/metabolism , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Circulating MicroRNA/blood , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/chemically induced , Diabetic Nephropathies/blood , Diabetic Nephropathies/etiology , Diabetic Nephropathies/pathology , Diet, High-Fat , Kidney/metabolism , Kidney/pathology , Lipids/blood , Male , Mice, Inbred C57BL , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Signal Transduction , Sirtuin 1/metabolism , Streptozocin
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(5): 520-526, 2018 May 20.
Article in Chinese | MEDLINE | ID: mdl-29891446

ABSTRACT

OBJECTIVE: To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice. RESULTS: Compared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFß1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice. CONCLUSIONS: Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.


Subject(s)
Diabetes Mellitus, Experimental/complications , Diabetic Cardiomyopathies/prevention & control , Exenatide/pharmacology , Hypoglycemic Agents/pharmacology , Sirtuin 1/metabolism , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/metabolism , Diet, High-Fat , Lipids/blood , Mice , Mice, Inbred C57BL , Oxidative Stress , Random Allocation , Transcription Factors/metabolism
3.
J Diabetes Res ; 2018: 3405695, 2018.
Article in English | MEDLINE | ID: mdl-29854821

ABSTRACT

BACKGROUND: NADPH oxidase 4 (NOX4) plays a major role in renal oxidative stress of diabetic kidney disease (DKD). NOX4 was significantly increased in Egr1-expressing fibroblasts, but the relationship between Egr1 and NOX4 in DKD is unclear. METHODS: For the evaluation of the potential relationship between Egr1 and NOX4, both were detected in HFD/STZ-induced mice and HK-2 cells treated with TGF-ß1. Then, changes in NOX4 expression were detected in HK-2 cells and mice with overexpression and knockdown of Egr1. The direct relationship between Egr1 and NOX4 was explored via chromatin immunoprecipitation (ChIP). RESULTS: We found increased levels of Egr1, NOX4, and α-SMA in the kidney cortices of diabetic mice and in TGF-ß1-treated HK-2 cells. Overexpression or silencing of Egr1 in HK-2 cells could upregulate or downregulate NOX4 and α-SMA. ChIP assays revealed that TGF-ß1 induced Egr1 to bind to the NOX4 promoter. Finally, Egr1 overexpression or knockdown in diabetic mice could upregulate or downregulate the expression of NOX4 and ROS, and α-SMA was also changed. CONCLUSION: Our study provides strong evidence that Egr1 is a transcriptional activator of NOX4 in oxidative stress of DKD. Egr1 contributes to DKD by enhancing EMT, in part by targeting NOX4.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Early Growth Response Protein 1/metabolism , NADPH Oxidase 4/metabolism , Oxidative Stress/physiology , Actins/genetics , Actins/metabolism , Animals , Cell Line , Diabetes Mellitus, Experimental/genetics , Diabetic Nephropathies/genetics , Down-Regulation/drug effects , Early Growth Response Protein 1/genetics , Kidney/drug effects , Kidney/metabolism , Male , Mice , NADPH Oxidase 4/genetics , Oxidative Stress/drug effects , Promoter Regions, Genetic , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta1/pharmacology , Up-Regulation/drug effects
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(8): 1054-1059, 2017 Aug 20.
Article in Chinese | MEDLINE | ID: mdl-28801285

ABSTRACT

OBJECTIVE: To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT). METHODS: This retrospective study was conducted in patients with adrenal lesions detected by abdominal CT examinations in Nanfang Hospital between July, 2014 and June, 2015. The clinical data of the patients were collected for analysis of the demographics, comorbidities, imaging characteristics, biochemical profiles, clinical diagnosis and intervention. RESULTS: A total of 939 patients with adrenal lesions were identified from 19 004 patients undergoing abdominal CT scan over the defined period. The mean age of the patients was 53.2 years and 560 of the patients were male. Among the total cases with adrenal lesions, the percentages of cases with adrenal masses tended to increase progressively with age. Endocrine studies were done in 270 of the total patients, which identified non-functioning masses in 38.9%, primary aldosteronism in 16.3%, Cushing's syndrome in 4.1%, subclinical Cushing's syndrome in 7.0%, and pheochromocytomas in 7.0% of the cases. Adrenal incidentalomas was detected in 191 patients, with a detection rate of 1.0% among the overall patients undergoing abdominal CT scans. Imaging study detected adenomas (70.3%), cortical carcinomas (2.4%), and metastases (0.5%). Of 191 patients with adrenal incidentalomas, only 76 (39.8%) underwent endocrine evaluation, including 34 with nonfunctioning adrenal masses, 17 with pheochromocytoma, 7 with primary aldosteronism, and 5 with subclinical Cushing's syndrome. CONCLUSION: s The overall detection rates of adrenal lesions and adrenal incidentalomas by abdominal CT were 4.9% and 1.0%, respectively, in our cohort of patients undergoing the examination over the defined period. Although most of the lesions were benign and nonfunctioning, malignant and functional lesions were also detected. As many as 60% of the patients with adrenal incidentalomas did not have hormonal testing. Clinicians need to have greater awareness of adrenal incidentalomas and standard protocol for its management should be established.

5.
Biochem Biophys Res Commun ; 487(2): 216-222, 2017 05 27.
Article in English | MEDLINE | ID: mdl-28411025

ABSTRACT

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-ß1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-ß1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-ß1/Smad3 signaling in DKD is unclear. In the present study, we assessed human MCs that were incubated under high-glucose conditions to mimic diabetes. Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN), collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and protein expression levels were determined by RT-qPCR and western blotting respectively. High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p-Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up-regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover, the effects of si-Klotho on Egr-1 expression were abolished by the TGF-ß1 inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production in high-glucose-treated human MCs, an effect that has been partially attributed to Egr-1 down-regulation facilitated by TGF-ß1/Smad3 signaling inhibition.


Subject(s)
Early Growth Response Protein 1/metabolism , Glucose/administration & dosage , Glucuronidase/metabolism , Mesangial Cells/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Cells, Cultured , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Down-Regulation/physiology , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Gene Knockdown Techniques , Glucuronidase/genetics , Klotho Proteins , Mesangial Cells/drug effects , Signal Transduction/drug effects , Signal Transduction/physiology
6.
Cell Signal ; 31: 96-104, 2017 02.
Article in English | MEDLINE | ID: mdl-28077323

ABSTRACT

Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor ß1 (TGF-ß1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells. We then found that miR-181a-5p expression was down-regulated, accompanied by the corresponding up-regulation of Egr1, TGF-ß1, fibronectin and collagen I in renal tissues of type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty rats with DN, and that the expression of miR-181a-5p was negatively correlated with the level of Egr1 in HK-2 cells treated with high glucose. Furthermore, we identified that miR-181a-5p directly suppressed Egr1 to decrease the expressions of TGF-ß1, fibronectin and collagen I in HK-2 cells through targeting the 3' untranslated region of Egr1. The functional relevance of miR-181a-5p-induced Egr1 decrease was supported by inhibition and overexpression of miR-181a-5p in HK-2 cells. Thus, we concluded that aberrant Egr1 expression, which can be suppressed by miR-181a-5p directly, plays a crucial role in the progression of renal TIF in DN. This study indicates that targeting miR-181a-5p may be a novel therapeutic approach of DN.


Subject(s)
Down-Regulation/genetics , Early Growth Response Protein 1/metabolism , Glucose/toxicity , Kidney Tubules, Proximal/pathology , MicroRNAs/genetics , 3' Untranslated Regions/genetics , Animals , Base Sequence , Cell Line , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Diabetic Nephropathies/genetics , Diabetic Nephropathies/pathology , Down-Regulation/drug effects , Early Growth Response Protein 1/genetics , Fibrosis , Humans , Male , MicroRNAs/metabolism , Rats, Inbred OLETF , Time Factors , Transforming Growth Factor beta1/pharmacology , Up-Regulation/drug effects
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(3): 371-4, 2016 Mar.
Article in Chinese | MEDLINE | ID: mdl-27063165

ABSTRACT

OBJECTIVE: To explore effects of exendin-4 on the metabolism of extracellular matrix (ECM) in human mesangial cells (HMC) cultured in the presence of high glucose and explore the possible mechanism. METHODS: Human mesangial cells (HMC) were treated with exendin-4 under high glucose conditions. The cell proliferation was observed using CCK8 assay, and the expressions of collagen type I, fibronectin, transforming growth factor-ß1 (TGFß1) expression and extracellular signal- regulated kinase (ERK) signaling pathway activity were assessed using Western blotting. RESULTS: Exendin-4 inhibited cell proliferation and the expressions of collagen type I, fibronectin and TGFß1 and reversed ERK phosphorylation in high glucose-induced HMC. CONCLUSION: Exendin-4 can regulate ECM metabolism in HMC cultured in high glucose by inhibiting TGFß1/ERK pathway, suggesting the beneficial effects of exendin-4 in preventing and treating diabetic nephropathy.


Subject(s)
Extracellular Matrix/metabolism , Mesangial Cells/drug effects , Peptides/pharmacology , Venoms/pharmacology , Cell Proliferation , Cells, Cultured , Collagen Type I/metabolism , Culture Media/chemistry , Diabetic Nephropathies , Exenatide , Fibronectins/metabolism , Glucose/chemistry , Humans , MAP Kinase Signaling System , Phosphorylation , Signal Transduction , Transforming Growth Factor beta1/metabolism
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(4): 563-566, 2016 Apr 20.
Article in Chinese | MEDLINE | ID: mdl-28446415

ABSTRACT

OBJECTIVE: To investigate the expressions of inflammation- and fibrosis-related genes in perinephric and subcutaneous adipose tissues in patients with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. METHODS: The perinephric and subcutaneous adipose tissues adipose tissues were obtained from 8 patients with ACTH-independent Cushing's syndrome undergoing laparoscopic retroperitoneal adrenalectomy. Real-time PCR was used to detect the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metallopeptidase 2 (MMP-2), TIMP metallopeptidase inhibitor 1 (TIMP-1), early growth response 1 (EGR1), CCAAT/enhancer binding protein ß(CEBPß), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA). RESULTS: The mRNA level of CIDEA was significantly higher in the perinephric adipose tissue (peri-N) than in the subcutaneous adipose tissue (subQ) (P<0.05). The expressions of CEBPß, UCP-1, and PGC1α mRNA in the peri-N were similar with those in the subQ. The expressions of IL-6, TIMP1 and EGR1 mRNA in the subQ were significantly higher than those in the peri-N (P<0.05). No significant difference in TNF-α and MMP-2 mRNA levels was found between peri-N and subQ. CONCLUSION: The expression levels of the inflammation- and fibrosis-related genes are higher in the subQ than in the peri-N of patients with ACTH-independent Cushing's syndrome, suggesting that chronic exposure to endogenous hypercortisolism may cause adipose tissue dysfunction.


Subject(s)
Adrenocorticotropic Hormone , Cushing Syndrome/metabolism , Subcutaneous Fat/metabolism , Adrenalectomy , CCAAT-Enhancer-Binding Protein-beta/metabolism , Cushing Syndrome/surgery , Early Growth Response Protein 1/metabolism , Humans , Matrix Metalloproteinase 2/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Real-Time Polymerase Chain Reaction , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Uncoupling Protein 1/metabolism
9.
Cell Physiol Biochem ; 36(6): 2093-107, 2015.
Article in English | MEDLINE | ID: mdl-26279418

ABSTRACT

UNLABELLED: Backgroud: Diabetic nephropathy is one of the most frequent causes of end-stage renal disease and is associated with proliferation of glomerular mesangial cells (MCs) and excessive production of the extracellular matrix (ECM). Several studies have shown that early growth response factor 1 (Egr1) plays a key role in renal fibrosis by regulating the expression of genes encoding ECM components. However, whether Egr1 also contributes to diabetic nephropathy is unclear. METHODS: In the present study, we compared the expression of Egr1 in kidneys from OLETF rats with spontaneous type 2 diabetes and healthy LETO rats. We also examined whether high glucose and TGF-ß1 signaling up-regulated Egr1 expression in cultured MCs, and whether Egr1 expression influenced MC proliferation and expression of ECM genes. RESULTS: We found that higher expression of Egr1 and TGF-ß1, at both the mRNA and protein levels, the kidneys from OLETF rats vs. LETO rats. High glucose or TGF-ß1 signaling rapidly up-regulated expression of Egr1 mRNA and protein in cultured MCs. Overexpressing Egr1 in MCs by transfection with M61-Egr1 plasmid or treatment with high glucose up-regulated expression of fibronectin, type IV collagen and TGF-ß1, and promoted MC proliferation. Conversely, siRNA-mediated silencing of Egr1 expression down-regulated these genes and inhibited MC proliferation. Chromatin immunoprecipitation (ChIP) assays revealed that Egr1 bound to the TGF-ß1 promoter. CONCLUSION: Our results provide strong evidence that Egr1 contributes to diabetic nephropathy by enhancing MC proliferation and ECM production, in part by interacting with TGF-ß1.


Subject(s)
Early Growth Response Protein 1/metabolism , Glucose/pharmacology , Kidney Glomerulus/pathology , Mesangial Cells/metabolism , Animals , Cell Proliferation/drug effects , Cells, Cultured , Chromatin Immunoprecipitation , Collagen Type IV/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Extracellular Matrix/metabolism , Fibronectins/metabolism , Fibrosis , Gene Expression Regulation/drug effects , Mesangial Cells/drug effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , RNA, Small Interfering/metabolism , Rats, Inbred OLETF , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology
10.
Mol Cell Biochem ; 393(1-2): 247-54, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24771016

ABSTRACT

The purposes of this study were to examine whether thermogenesis in 3T3-L1 adipocytes is related to variations in thyroid hormone receptors (TRs) that are differently regulated by triiodothyronine (T3), and the possible role of AMP-activated protein (AMPK) in thermogenesis after cell differentiation. Differentiated 3T3-L1 adipocytes were maintained under four conditions: normal control group, T3 treatment group, AMPK agonist (5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside) treatment group, and T3 and AMPK inhibitor (Compound C) treatment group. Real-time polymerase chain reaction was then performed to evaluate the changes in TRα and TRß mRNA levels in the cells, as well as marker genes for brown adipose tissue including uncoupling protein (UCP)-1 and Cidea. Western blotting was carried out for the cells to detect the expressions of TRα, TRß, and AMPK protein levels. After T3 treatment, the mRNA and protein levels of TRα decreased compared with the control group, while TRß mRNA and protein levels increased markedly at the same time. We also found elevated mRNA levels of UCP-1 and Cidea after exposure to T3. However, the distribution of TRs was reversed by Compound C. AMPK protein levels were clearly activated by T3. Our results suggest that the distribution of TRs is related to thermogenesis, and AMPK may participate in the alterations.


Subject(s)
AMP-Activated Protein Kinases/genetics , Ion Channels/biosynthesis , Mitochondrial Proteins/biosynthesis , Receptors, Thyroid Hormone/metabolism , Thermogenesis/genetics , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Animals , Cell Differentiation , Gene Expression Regulation, Developmental/drug effects , Mice , RNA, Messenger/biosynthesis , Triiodothyronine/administration & dosage , Uncoupling Protein 1
11.
Cell Physiol Biochem ; 33(2): 423-32, 2014.
Article in English | MEDLINE | ID: mdl-24556697

ABSTRACT

BACKGROUND/AIMS: Glucagon-like peptide-1 (GLP-1), which counteracts insulin resistance in humans with type 2 diabetes, has been shown to ameliorate diabetic nephropathy in experimental models. However, the mechanisms through which GLP-1 modulates renal function remained illdefined. The present study investigated the putative mechanisms underlying effects of exendin-4, a GLP-1 analog, on mesangial cell proliferation and fibronectin. METHODS: Rat mesangial cells (MCs) were treated with exendin-4 under high glucose conditions. AMP-activated protein kinase (AMPK) inhibitors (compound C) and agonists (AICAR) were used to analyze the role of this kinase. Cell proliferation was measured using a MTT assay. Fibronectin expression and AMPK-signaling pathway activity were assessed using ELISA and Western blotting, respectively. The production of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2 was evaluated using quantitative real-time RT-PCR. RESULTS: Exendin-4 inhibited cell proliferation and fibronectin secretion in high glucose-induced MCs. It also caused phosphorylation of AMPK and subsequently increased the ratio of MMP-2 to TIMP-2, which resulted in the degradation of fibronectin. Exendin-4 reversed extracellular signal-regulated kinase (ERK) phosphorylation and enhanced expression of mammalian target of rapamycin (mTOR) in MCs. Moreover, the activation of the AMPK pathway by exendin-4 was induced by AICAR, which was inhibited by compound C. CONCLUSION: Exendin-4 exerts an inhibitory effect on cell proliferation and fibronectin secretion in rat MCs, partly through AMPK activation. These results may explain some of the beneficial effects of exendin-4 on the kidney.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Diabetic Nephropathies/enzymology , Glucose/pharmacology , Hypoglycemic Agents/pharmacology , MAP Kinase Signaling System/drug effects , Peptides/pharmacology , Sweetening Agents/pharmacology , Venoms/pharmacology , AMP-Activated Protein Kinases/genetics , Animals , Cell Proliferation/drug effects , Diabetic Nephropathies/pathology , Exenatide , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Glucose/metabolism , MAP Kinase Signaling System/genetics , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 2/genetics , Mesangial Cells , Rats , Sweetening Agents/metabolism , TOR Serine-Threonine Kinases/biosynthesis , TOR Serine-Threonine Kinases/genetics
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(10): 2330-2, 2010 Oct.
Article in Chinese | MEDLINE | ID: mdl-20965838

ABSTRACT

OBJECTIVE: To study the effect of heme oxygenase-1(HO-1) on proteins related to apoptosis in INS-1 cells with exposure to intermittent high glucose. METHODS: INS-1 cells cultured in vitro were divided into control group, persistent high glucose group (PHG), intermittent high glucose group (IHG), CoPP + intermittent high glucose group (CoPP+IHG), and ZnPP+ intermittent high glucose group (ZnPP+IHG). After 72 h of treatment with the corresponding protocols, the cells were examined for expressions of HO-1 protein by Western blotting and for expressions of Bax and Bcl-2 by immunocytochemistry. RESULTS: In comparison with the control group, the cells in both PHG group and IHG group showed significantly increased expressions of HO-1 (P<0.01) and decreased Bcl-2/Bax ratios (P<0.05). The cells in CoPP+ IHG group exhibited a greater HO-1 protein expression but a lower Bcl-2/Bax ratio than those in IHG group (P<0.05) The ZnPP+IHG group demonstrated opposite changes in terms of HO-1, Bax and Bcl-2 expressions compared with the CoPP+IHG group. CONCLUSION: Intermittent high glucose can lower Bcl-2/Bax ratio in INS-1 cells, and HO-1 may protect INS-1 cells against apoptosis possibly by up-regulating the Bcl-2/Bax ratio.


Subject(s)
Apoptosis/drug effects , Glucose/adverse effects , Heme Oxygenase (Decyclizing)/metabolism , Islets of Langerhans/drug effects , Animals , Caspase 3/metabolism , Cell Line , Glucose/administration & dosage , Islets of Langerhans/cytology , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , bcl-2-Associated X Protein/metabolism
14.
Di Yi Jun Yi Da Xue Xue Bao ; 25(2): 234-5, 2005 Feb.
Article in Chinese | MEDLINE | ID: mdl-15699016

ABSTRACT

OBJECTIVE: To investigate the prevalence of microalbuminuria in type 2 diabetic patients with hypertension. METHOD: Urinary albumin excretion was measured in 55 diabetic patients with hypertension by colorimetric methods using commercially available test strips of Nephur 7 and Micro-II, the latter test strips employed only when the former yielded negative results for proteinuria. The height, body weight, waist circumference and blood pressure were measured for all the patients with also biochemical examination for serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, blood glucose and creatinine. HbA1c was determined by Bio-STAT. RESULTS: The rates of normal urinary albumin, micro- and macroalbuminuria were 66.67%, 22.22% and 11.11% in these patients, respectively. In patients with a history of diabetes for more than 10 years, the rates were 58.33%, 8.33% and 33.33%, respectively. CONCLUSION: Nearly 1/3 of type 2 diabetic patients with hypertension have microalbuminuria and proteinuria, and screening for microalbuminuria and proper interventions in these patients might prove beneficial.


Subject(s)
Albuminuria/epidemiology , Diabetes Mellitus, Type 2/complications , Hypertension/complications , Albuminuria/etiology , China/epidemiology , Female , Humans , Male , Prevalence
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 30(6): 704-7, 2005 Dec.
Article in Chinese | MEDLINE | ID: mdl-16708815

ABSTRACT

OBJECTIVE: To determine the changes of advanced oxidation protein products (AOPP) in diabetic nephropathy (DN) patients, as well as its relationship with superoxide dismutase (SOD), glutathione peroxidase (GPx) and neopterin (NPT). METHODS: By the concentration of urinary albumin excretion rate (UAER) and creatinine (Cr), 85 diabetes mellitus (DM) patients were divided into 4 groups as non-DN group (DM), early-staged DN group (DN3), significant DN group (DN4) and end-staged DN group (DN5). The concentration of the serum AOPP was measured by ameliorated method introduced by Wikto-Sarsat, while SOD by Xanthine oxidase test, GPx by [5,5'Dithio-bis (2-Nitrobenzoic aicd) ] (DTNB) reaction test and NPT by ELISA. RESULTS: AOPP in Group DN5 [(117.8 +/- 64.8) [micromol/L] and Group DN4 [ (80.0 +/- 23.0) micromol/L] were significantly higher than those in Group DM [(58.2 +/- 17.7) micromol/L]. There was no significant difference of AOPP between Group DN3 [(72.7 +/-17.2) micromol/L] and Group DM. Serum AOPP negatively correlated with SOD and GPx (r = -0.217 and -0.374 respectively, P < 0.05), while positively correlated with NPT (r = 0.499, P < 0.01). CONCLUSION: DN patient has enhanced protein oxidation than DM patient, which is related to oxidative stress and chronic inflammation in DN.


Subject(s)
Diabetic Nephropathies/blood , Glutathione Peroxidase/blood , Neopterin/blood , Oxidative Stress , Superoxide Dismutase/blood , Aged , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Middle Aged , Oxidation-Reduction
17.
Di Yi Jun Yi Da Xue Xue Bao ; 23(11): 1191-3, 2003 Nov.
Article in Chinese | MEDLINE | ID: mdl-14625185

ABSTRACT

OBJECTIVE: To investigate the relationship between angiotensinogen (AGT) gene polymorphism and hypertension in type 2 diabetic patients. METHODS: A total of 240 patients with type 2 diabetes mellitus were divided into normotensive and hypertensive groups according to their blood pressure measurement, and their fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein and very-low-density lipoprotein were measured. The AGT genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distributions of AGT genotypes in normotensive and hypertensive groups were similar, and the frequency of M allele in female hypertensive patients was significantly higher than that in female normotensive patients. CONCLUSION: The M allele of AGT gene is probably related to hypertension in female type 2 diabetic patients.


Subject(s)
Angiotensinogen/genetics , Diabetes Mellitus, Type 2/genetics , Hypertension/genetics , Polymorphism, Genetic , Adult , Aged , Diabetes Mellitus, Type 2/complications , Female , Genotype , Humans , Hypertension/etiology , Male , Middle Aged
18.
Di Yi Jun Yi Da Xue Xue Bao ; 22(1): 70-1, 2002 Jan.
Article in Chinese | MEDLINE | ID: mdl-12390852

ABSTRACT

OBJECTIVE: To investigate the association of hyperuricemia with the incidence of stroke in type 2 diabetic patients. METHODS: Sixty type 2 diabetic patients with stroke, 75 patients with simple stoke and 67 simple type 2 diabetic patients were randomly selected from the hospitalized patients. The serum levels of uric acid (UA), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol(LDL), very-low-density lipoproteincholesterol (VLDL) and high-density lipoprotein- cholesterol (HDL) of all the patients were determined and comparison between the groups performed. RESULTS: Male type 2 diabetic patients with stroke had significantly higher mean levels of serum uric acid than simple diabetic patients, but such patients of both genders all had lower HDL levels. CONCLUSION: The decreased serum HDL level poses as an important risk factor for stroke in all type 2 diabetic patients, among whom the male patients in particular have hyperuricemia as another important risk factor for stroke.


Subject(s)
Diabetes Mellitus, Type 2/blood , Stroke/complications , Uric Acid/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cholesterol, VLDL/blood , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...