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>

Pathogen analysis in patients with diabetic foot osteomyelitis using 16S rRNA high-throughput sequencing / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the characteristics of pathogenic microorganisms in the infected bone tissues in patients with diabetic foot osteomyelitis (DFO) using 16S rRNA high-throughput sequencing to facilitate rapid and accurate detection of pathogens and effective infection control.</p><p><b>METHODS</b>Between September, 2016 and April, 2017, 16 patients with DFO were admitted in our department and infected bone specimens were obtained during debridement. The pathogenic microorganisms in the specimens were identified using both 16S rRNA high-throughput sequencing and automatic blood culture analyzer, and the characteristics of the microflora were analyzed based on 16S rRNA sequencing data in comparison with the results of blood culture.</p><p><b>RESULTS</b>The results of 16S rRNA sequencing showed that bone tissues of DFO contained diverse and uniformly distributed pathogenic organisms, among which 20 (87%) dominant genera were identified with Prevotella as the most abundant pathogen. Both 16S rRNA sequencing and routine culture results suggested the domination of gram-negative bacteria among the pathogens in DFO bone tissues. 16S rRNA sequencing, compared with routine culture, yielded a higher positivity rate (100% vs 88.24%) and detected a greater average number of pathogens (12.56 vs 1.50) and a higher proportion of gram-negative bacteria (67.16% vs 50.00%) in the samples. 16S rRNA sequencing detected nearly all the pathogens identified by routine culture except for Escherichia coli, Serratia marcescens and Enterobacter cloaca, and identified 13 genera that failed to be detected by routine culture, including the obligate or strict anaerobes Anaerococcus, Veillonella, Bacteroides, Fusobacterium, Porphyromonas, Finegoldia, Prevotella, Peptostreptococcus, Parvimonas, Peptoniphilus and Bulleidia. Routine culture did not detect any anaerobes in the samples but identified multidrug-resistant strains in as many as 58.33% of the pathogens.</p><p><b>CONCLUSIONS</b>16S rRNA high-throughput sequencing is capable of demonstrating the diversity and abundance of microflora in DFO bone tissues, where diverse and uniformly distributed pathogens can be detected with a discrete distribution of the dominant genera, most of which are gram-negative. Compared with routine culture method, 16S rRNA sequencing allows more convenient and accurate identification of the pathogens (especially gram-negative bacteria and anaerobes), and can be useful in clinical decision on appropriate treatment of DFO.</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>

Anlysis of foot biomechanics characteristic in 303 patients with type 2 diabetes mellitus / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus.</p><p><b>METHODS</b>This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system.</p><p><b>RESULTS</b>The maximum peak pressure of 10 regions decreased in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the left foot, and in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the right foot. The MPP in M1 region was higher in the right than in the left foot (P<0.05). The MPP in M3, M4, M5, and MF was higher in the left than in the right foot (P<0.05). The percentage of high-risk foot (defined by a total plantar pressure ≥70 N/cm) was 34% on the left and 17.7% on the right. An increased BMI was associated with a significant increase in high-risk foot, but not for the right foot in underweight patients. Foot flat phase was extended and forefoot push-off phase shortened in stance phase in the patients. Compared with the right foot, the left foot showed a significantly increased foot arch index and increased low and high arch rates with a decreased normal arch rate. Total plantar pressure was higher in of the left high arch foot than in normal arch foot. The foot angle was significantly larger on the right than on the left. The bilateral total plantar pressures were significantly greater in male patients (P<0.05) and increased with age but were not associated with the duration of DM, foot angle, or glycosylated hemoglobin level.</p><p><b>CONCLUSION</b>Diabetic patients have obvious alterations in foot biomechanics with abnormalities of the plantar pressure, and the percentage of high-risk foot increases in overweight and obese patients, suggesting the need of body weight control in these patients when administering offloading treatment for prevention of diabetic foot ulcer.</p>

Blue rubber bleb nevus syndrome complicated by a ventricular septal defect: a case report / 南方医科大学学报

The co-occurrence of blue rubber bleb nevus syndrome (BRBNS) and ventricular septal defects is rare. Here we present a case of BRBNS in a 15-year-old boy who was born with multiple cavernous hemangiomas and a ventricular septal defect. Examinations revealed the presence of hemangioma lesions in the subcutaneous and mucosal tissues as well as in the cerebrum, nasopharynx, tongue, esophagus, gastric body, sigmoid colon and adrenal gland. Combined imaging modalities played an important role in the diagnosis of hemangioma lesions.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>

Effect of HbA1c combined FPG on screening diabetes in health check-up

OBJECTIVE@#To appraise the effectiveness of HbA(1c) and fasting plasma glucose (FPG) on screening diabetes in health check-up.@*METHODS@#A total of 1,337 individuals (male 850, female 487), aged 27 to 91 years with HbA(1c) test were included. Participates with HbA(1c) ≥6.0% or FPG≥6.1 mmol/L underwent oral glucose tolerance test (OGTT). Diabetes mellitus was diagnosed according to the criteria of WHO in 1999, FPG≥7.0 mmol/L and/or OGTT 2 h-postload plasm glucose (2 h-PG)≥11.1 mmol/L. The sensitivity and specificity of HbA(1c) thresholds and FPG or combination test on screening of diabetes were analyzed.@*RESULTS@#A total of 842 subjects had HbA(1c) <6.0%, in which 32 had isolated FPG≥6.1 mmol/L, of 495 had HbA(1c)≥6.0%. Subjects with HbA(1c)≥6.0% had significant increased disorder indexes than those with HbA(1c)<6.0%. 527 subjects who had HbA(1c)≥6.0% or FPG≥6.1 mmol/L underwent OGTT. A total of 234 subjects were newly diagnosed diabetes, including 123 (123/234, 52.56%) with FPG≥7.0 mmol/L, and 111 subjects (111/234, 47.43%) with isolated 2 h-PG≥11.1 mmol/L. Among 234 new diabetes, 91.88% (215 subjects) had HbA(1c)≥6.3%, and 77.40% (181 subjects) had HbA(1c)≥6.5%. HbA(1c)≥6.3% combined FPG ≥7.0 mmol/L increased the positive rate of newly diagnosed diabetes from 91.88% to 96.58%.@*CONCLUSIONS@#HbA(1c) is a practical and convenient tool for screening undiagnosed diabetes in routine health check-up of a large population. Combined use of HbA(1c)≥6.3% and/or FPG≥7.0 mmol/L is efficient for early detection of diabetes.

Cellular memory of high glucose exposure in normoglycemia is probably mediated by reactive oxygen species in INS-1 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the cellular memory of previous high glucose exposure in rat islet cell line (INS-1) and explore the possible mechanism.</p><p><b>METHODS</b>INS-1 cells were exposed to a high glucose (33.3 mmol/L) culture for 48 h followed by further culture in the presence of 11.1 mmol/L glucose in the culture medium for 3 or 5 days. The levels of bax and caspase-3 mRNA were measured by real-time PCR, the production of reactive oxygen species (ROS) was assayed using the dihydroethidium probe, and the cell viability was detected by MTT assay.</p><p><b>RESULTS</b>High glucose exposure of the cells for 48 h resulted in significantly increased ROS production and bax and caspase-3 mRNA expressions and lowered cell viability (P<0.001). In cells cultured in 11.1 mmol/L glucose following previous high glucose exposure, the ROS production and bax and caspase-3 mRNA expressions still maintained the high levels (P<0.05) while the cell viability remained significantly lower than the control cells (P<0.001).</p><p><b>CONCLUSION</b>High glucose causes persistent changes in cell viability and apoptosis-related gene expressions even after recovery of normoglycemia, the mechanism of which is probably related to increased ROS production.</p>

Adiponectin decreases insulin receptor substrate-1 phosphorylation in the liver of OLETF rats possibly through nuclear factor-κB signaling pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of adiponectin (APN) on the insulin pathway in the liver of OLETF rats and explore its molecular mechanism.</p><p><b>METHODS</b>Twenty male OLETF rats and 10 male LETO rats were sacrificed at 8 and 32 weeks of age to examine the fasting blood glucose, serum insulin, adiponectin and blood lipid profiles. The APN, phosphotyrosine of insulin receptor substrate-1 (IRS-1), IKKβ and nuclear-κB (NF-κB) in the liver tissue were determined using ELISA, Western blotting or immunohistochemistry.</p><p><b>RESULTS</b>The plasma adiponectin level in OLETF rats was significantly lower than that of LETO rats since 8 weeks of age (P<0.01). At 32 weeks of age, the blood lipid levels of OLETF rats increased significantly (P<0.05) with inverse correlations to plasma adiponectin (P<0.01). The liver APN, py-IRS-1, IKKβ and NF-κB levels in OLETF rats differed significantly from those of LETO rats at both 8 and 32 weeks. At 32 weeks of age, the APN level of both rats were correlated to the levels of NF-κB and py-IRS-1 (P<0.01).</p><p><b>CONCLUSION</b>APN may decrease tyrosine phosphorylation of IRS-1 via the IKK/NFκB pathway and inhibit insulin signaling pathway in the liver, which contributes to hyperlipidemia, hyperglycemia and development of type 2 diabetes.</p>

Hypoadiponectinemia leads to insulin resistance in OLETF rats: a preliminary study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between plasma adiponectin and insulin resistance in OLETF rats.</p><p><b>METHODS</b>Twenty male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and 10 male Long-evans Tokushima Otsuka (LETO) rats underwent oral glucose tolerance test (OGTT) at 13 and 40 weeks of age. At 8, 32 and 40 weeks of age, the rats were sacrificed to measure the blood glucose, plasma insulin and adiponectin levels, and serum levels of TG, CHOL and FFA.</p><p><b>RESULTS</b>The plasma adiponectin level was significantly decreased in 8-week-old OLETF rats compared with that of LETO rats (P<0.05). The plasma insulin level, TG, CHOL, and FFA were significantly higher in OLETF rats than in LETO rats at 32 and 40 weeks of age.</p><p><b>CONCLUSION</b>A decreased plasma level of adiponectin preludes insulin resistance and is inversely correlated to insulin sensitivity. Hypoadiponectinemia may be an important reason leading to insulin resistance.</p>

Efficacy and safety evaluation of two insulin treatment protocols using a continuous glucose monitoring system / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of two insulin treatment protocols using a continuous glucose monitoring system.</p><p><b>METHODS</b>Type 2 diabetic patients mellitus with unsatisfactory control of fasting blood glucose by oral antidiabetic drugs were included in the study. The patients were randomized into two groups to receive bedtime injection of glargine and oral antidiabetic drugs (group A) or injection of Novolin 30 R twice a day (group B) for 12 weeks. The insuline dose was adjusted according to fasting blood glucose till discharge. Continuous glucose monitoring system was used to record the average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L%, HbA1c and C peptide, bedtime blood glucose, 3:00 AM blood glucose, the incidence of hypoglycemia and body mass index.</p><p><b>RESULTS</b>The average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L% and HbA1c was significantly decreased and C peptide significantly increased in the two groups after the treatments. The patients in glargine group showed better improvement with a significantly lower incidence of hypoglycemia than those in Novolin 30 R group. BMI underwent no significant changes in the two groups after the treatments.</p><p><b>CONCLUSION</b>Glargine therapy better mimics the physiological insulin secretion patterns, and when combined with oral antidiabetic drugs, can be more effective and safer than premixed insulin.</p>

Relationship between visceral fat depot and adiponectin mRNA level in the adipose tissue of OLETF rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between visceral fat depot and adiponectin level in OLETF rats.</p><p><b>METHODS</b>Twenty male OLETF rats and 10 male Long-Evans Tokushima Otsuka (LETO) rats were subjected to regular oral glucose tolerance test (OGTT). The rats were sacrificed at the ages of 8, 32 and 40 weeks for measurements of the body weight, blood glucose, blood lipid level, blood insulin, and weight of the visceral fat.</p><p><b>RESULTS</b>Compared with LETO rats, OLETF rats had significantly higher body weight and visceral fat with impaired glucose tolerance (P<0.05). OLETF rats also had higher blood insulin, TG, FFA and CHOL levels (P<0.05). The plasma adiponectin level was significantly lower in OLETF rats than in LETO rats at different ages (P<0.05). The adiponectin mRNA level in the adipose tissue of OLETF rats was comparable with that in LETO rats, but significantly decreased at 32 and 40 weeks of age (P<0.01).</p><p><b>CONCLUSION</b>Plasma adiponectin level is significantly correlated to insulin sensitivity and visceral fat depots in OLETF rats, but a lowered APN mRNA expression level is not the main reason for a decreased plasma adiponectin level in the early stage.</p>

Effect of short-term intensive therapy with glimepiride and metformin in newly diagnosed type 2 diabetic patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.</p><p><b>METHODS</b>Out-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.</p><p><b>RESULTS</b>After the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.</p><p><b>CONCLUSION</b>Short-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.</p>

High glucose induces INS-1 cell apoptosis by activating nuclear factor-κB / 南方医科大学学报

<p><b>OBJECTIVE</b>To study of the role of nuclear transcription factor-κB (NF-κB) in high glucose-induced apoptosis in INS-1 cells.</p><p><b>METHODS</b>Rat insulinoma (INS-1) cells cultured in RPMI 1640 medium were treated with 11.1 mmol/L glucose, 33.3 mmol/L glucose, or 33.3 mmol/L glucose plus 5 µmol/L NF-κB inhibitors for 48 h. The expression of NF-κB subunit P65 protein in the cell nuclei was detected by Western blotting, IKK belta mRNA level by quantitative RT-PCR, and cell apoptosis by Annexin V-PI double staining.</p><p><b>RESULTS</b>Compared with the control levels, IKK belta mRNA levels of the cells significantly increased in response to 33.3 mmol/L glucose exposure (P<0.01), which also resulted in significantly increased P65 protein expression in the cell nuclei (P<0.01) and cell apoptosis rate (P<0.05). Compared with those in the high glucose group, the expression of IKK belta mRNA and P65 protein and cell apoptosis rate decreased significantly after treatment with 33.3 mmol/L glucose plus 5 µmol/L NF-κB inhibitors (P<0.05).</p><p><b>CONCLUSION</b>High glucose induces NF-κB activation in INS-1 cells, and inhibition of NF-κB activation may protect INS-1 cells from high glucose-induced cell apoptosis.</p>

Reactive oxygen species participates in low glucose-induced injury of ECV304 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of low glucose-induced injury in human ECV304 cells.</p><p><b>METHODS</b>Human umbilical vein endothelial cell line ECV304 were stimulated with low concentrations of glucose. The level of reactive oxygen species (ROS) in cells was detected at different time points within 12 h by kinetic measurement of dichlorofluorescein (DCF) fluorescence produced by oxidation of an oxidant-sensitive dye 2,7-dichlorofluorescein (DCFH). ECV304 cell viability was assessed with MTT assay and NADPH oxidase activity detected using lucigenin-enhanced chemiluminescence assay following cell stimulation with low glucose and apocynin.</p><p><b>RESULTS</b>Low-glucose exposure of ECV304 cells time- and dose-dependently induced ROS production, and which was decreased by apocynin treatment. Apocynin pretreatment of the cells inhibited ROS production by 44% in cells exposed to 2.8 mmol/L glucose and by 60% in cells without glucose exposure.</p><p><b>CONCLUSIONS</b>Low glucose of ECV304 cells induces ROS production to cause cell injury, which is mediated partially by NADPH oxidase activation.</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>

Effects of Liuweidihuang pills on pancreatic islet structure in OLETF rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of Liuweidihuang pills on pancreatic islet structure in OLETF (Otsuka Long-Evans Tokushima Fatty) rats.</p><p><b>METHODS</b>Forty male OLETF rats were divided randomly into Liuweidihuang pills group (Liuwei group) and control group (n=20). Ten male LETO rats were used as normal control group (LETO group). The rats in Liuwei group were given Liuweidihuang pills at the daily dose of 2.4 mg/kg intragastrically since the age of 8 weeks. Blood glucose was determined by OGTT. The rats were sacrificed at 8, 32 and 40 weeks and the pancreatic tissue was isolated to examine the morphological changes of the pancreas by HE staining and Masson trichrome staining.</p><p><b>RESULTS</b>As the age of the rats increased, the pancreatic islets in the control group gradually showed fibrosis and islet atrophy, which were not found in Liuwei group. Masson staining visualized no fibrosis in Liuwei group. No significant pathological change occurred in the pancreatic islet of LETO rats. The rats in Liuwei group developed diabetes since 30 weeks of age and the incidence was 28.6% at 40 weeks, significantly lower than that in the control group (P<0.01).</p><p><b>CONCLUSION</b>Liuweidihuang pills can prevent degeneration of the pancreatic islets in spontaneous OLETF rats.</p>

Effects of metformin on proliferation of human colon carcinoma cell line SW-480 / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of metformin on the proliferation of SW-480 cells and study the possible mechanism.</p><p><b>METHODS</b>The proliferation of SW-480 cells treated with different concentrations of metformin was assessed by MTT assay, and the cell cycle changes were analyzed by flow cytometry. The expression of cyclin D1 in the treated cells was detected by Western blotting, and telomerase activity examined by telomeric repeat amplification protocol (TRAP) silver staining.</p><p><b>RESULTS</b>Metformin decreased the proliferation of SW-480 cells in a dose- and time-dependent manner. The proportion of the cells at G0/G1 stage in the control and metformin-treated (5 mmol/L, 72 h) cells was (55.81-/+0.63)% and (63.38-/+0.99)%, the cell proportion at S stage was (31.11-/+3.05)% and (25.29-/+1.64)%, and that at G2/M stage was (13.09-/+3.00)% and (11.33-/+2.60)%, respectively. The expression of cyclin D1 in metformin-treated cells were lowered significantly as compared with that in the control cells. Telomerase activity was also decreased significantly in the cells after treatment with 5 mmol/L metformin for 72 h.</p><p><b>CONCLUSION</b>Metformin can inhibit the growth of SW-480 cells mainly by blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and decreasing telomerase activity.</p>