Exendin-4 alleviates diabetic cardiomyopathy in mice by regulating Sirt1/PGC1α / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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, TGFβ1, 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, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.</p><p><b>CONCLUSIONS</b>Exendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.</p>

Clinical analysis of 939 patients with adrenal lesions detected by abdominal computed tomography / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the prevalence, etiology and clinical characteristics of adrenal lesions detected by abdominal computed tomography (CT).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Expressions of inflammatory and fibrogenic factors in perinephric and subcutaneous adipose tissues of patients with adrenocorticotropic hormone-independent Cushing's syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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 β(CEBPβ), uncoupling protein 1(UCP-1), PPARγ coactivator 1 alpha (PGC1α) and cell death-inducing DFFA-like effector a (CIDEA).</p><p><b>RESULTS</b>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 CEBPβ, 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.</p><p><b>CONCLUSION</b>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.</p>

Effects of exendin-4 on extracellular matrix metabolism in human mesangial cells cultured in high glucose / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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-β1 (TGFβ1) expression and extracellular signal- regulated kinase (ERK) signaling pathway activity were assessed using Western blotting.</p><p><b>RESULTS</b>Exendin-4 inhibited cell proliferation and the expressions of collagen type I, fibronectin and TGFβ1 and reversed ERK phosphorylation in high glucose-induced HMC.</p><p><b>CONCLUSION</b>Exendin-4 can regulate ECM metabolism in HMC cultured in high glucose by inhibiting TGFβ1/ERK pathway, suggesting the beneficial effects of exendin-4 in preventing and treating diabetic nephropathy.</p>

Effects of heme oxygenase-1 on proteins related to apoptosis in INS-1 cells exposed to intermittent high glucose / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Advanced oxidation protein products in diabetic nephropathy patients and its relation with superoxide dismutase, glutathione peroxidase, neopterin / 中南大学学报(医学版)

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.