The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer.

BACKGROUND: Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism. METHODS: The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease ≤ 4 weeks and the chronic wound (CW) group with the course of disease > 4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-κB (NF-κB), and interleukin-6 (IL-6) were detected by western blot. RESULTS: A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group (P < 0.05), and the expression of NF-κB and IL-6 was obviously increased (P < 0.05). CONCLUSION: The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.

The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE-/- Mice.

Background. Our study aimed to observe the effect of sodium glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin on diabetic atherosclerosis and investigate the subsequent mechanism. Methods. Aortic atherosclerosis was induced in streptozotocin induced diabetic ApoE-/- mice by feeding with high-fat diet, and dapagliflozin was administrated intragastrically for 12 weeks as treatment. Effects of dapagliflozin on indices of glucose and fat metabolism, IL-1ß, IL-18, NLRP3 protein levels, and the reactive oxygen species (ROS) were measured. The atherosclerosis was evaluated by oil red O and hematoxylin-eosin staining. The effects of dapagliflozin on the IL-1ß production in culturing primary macrophages of wild type and NLRP3-/- knockout mice were investigated for mechanism analyses. Results. Dapagliflozin treatment showed favorable effects on glucose and fat metabolism, partially reversed the formation of atherosclerosis, inhibited macrophage infiltration, and enhanced the stability of lesion. Also, reduced production of IL-1ß, IL-18, NLRP3 protein, and mitochondrial ROS in the aortic tissues was detected with dapagliflozin treatment. In vitro, NLRP3 inflammasome was activated by hyperglucose and hyperlipid through ROS pathway. Conclusions. Dapagliflozin may be of therapeutic potential for diabetic atherosclerosis induced by high-fat diet, and these benefits may depend on the inhibitory effect on the secretion of IL-1ß by macrophages via the ROS-NLRP3-caspase-1 pathway.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Improving insulin self-injection accuracy in patients with diabetes mellitus through a nursing project.

BACKGROUND: Non-standardized insulin injection has an impact on the efficacy of glucose control. OBJECTIVES: The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients. MATERIAL AND METHODS: A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge. RESULTS: Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group. CONCLUSIONS: The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.

Sex Differences in Type 2 Diabetes Mellitus-Related Left Ventricular Remodeling: A Cardiovascular Magnetic Resonance Study.

Background: The purpose of this study was to evaluate the sex differences in myocardial structure, tissue characteristics, and myocardial function in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 62 T2DM patients and 40 controls were prospectively recruited for the study. All the participants were scanned using cardiovascular magnetic resonance (CMR) cine and underwent native and postcontrast T1 mapping to obtain left ventricular (LV) structure, function, and tissue characteristics. The differences between the control and T2DM patients were compared in males and females, respectively. Results: For myocardial structure, T2DM was associated with a larger ratio of myocardial mass to end-diastolic volume (MVR, T2DM: 0.87 ± 0.20 vs. controls: 0.73 ± 0.14, p = 0.008) and thicker wall thickness (WT, T2DM: 6.5 ± 1.1 mm vs. controls: 5.6 ± 1.0 mm, p = 0.002) in females. For tissue characteristics, T2DM was associated with a similar T1 value, elevated extracellular volume fraction (ECV, T2DM: 27.8 ± 3.6% vs. controls: 25.1 ± 2.5%, p = 0.002), and increased extracellular matrix volume index (ECMVi, T2DM: 15.8 ± 3.8 ml/m2 vs. controls: 13.4 ± 2.7 ml/m2, p = 0.008) in males. For myocardial function, in male, compared with control, T2DM was associated with decreased peak longitudinal diastolic strain rate (PLDSR, T2DM: 0.97 ± 0.19 1/s vs. control: 1.13 ± 0.29 1/s, p = 0.030). Conclusions: There might be sex differences in myocardial remodeling induced by T2DM, including LV structural concentric remodeling in female patients and extracellular matrix remodeling and subclinical diastolic dysfunction in male patients.

Assessment of right ventricular function using cardiovascular magnetic resonance in patients with type 2 diabetes mellitus.

BACKGROUND: Accurate evaluation of right ventricular (RV) function is always difficult due to its irregular shape and movement. Many indices have been proposed to assess RV function, but none have been universally accepted. This study evaluated RV function in type 2 diabetes mellitus (T2DM) patients using long-axis strain (LAS) and other traditional indices. METHODS: Fifty-seven patients with T2DM and 39 healthy controls were prospectively enrolled. Four-chamber cardiovascular magnetic resonance (CMR) and RV short-axis cine images were obtained from all participants to measure the tricuspid annular plane systolic excursion (TAPSE), RV ejection fraction (EF), peak longitudinal strain (PLS) and four LAS indices. The inter-and intraobserver variabilities were also calculated. RESULTS: Compared with healthy controls, T2DM was associated with a decreased LAS (apex/lateral wall) (-17.4%±4.2% vs. control, -19.7%±3.7%, P=0.008) and LAS (apex/middle point) (-17.5%±4.5% vs. control, -19.5%±3.9%, P=0.026), but both groups had a similar LAS (RV/lateral wall) and LAS (RV/middle point) (all P>0.05). After adjustments for age and body mass index, a significant difference was observed only for LAS (apex/lateral wall) (P=0.028). There were no significant differences in the TAPSE, RVEF and PLS (all P>0.05). LAS (apex/lateral wall) correlated with the TAPSE (r=-0.723, P<0.001), RVEF (r=-0.270, P=0.008) and PLS (r=0.210, P=0.040). The inter- and intraobserver variability of the LAS (apex/lateral wall) were lower than the other three LAS indices. CONCLUSIONS: Compared with traditional RV function indices, such as the TAPSE, RVEF and PLS, LAS is easy to obtain and shows high repeatability. LAS (apex/lateral wall) may provide a more sensitive T2DM-related RV dysfunction index.

Metformin and Malignant Tumors: Not Over the Hill.

Malignant tumors are a major cause of death, and their incidence is increasing worldwide. Although the survival rate for some cancers has improved, treatments for other malignant tumors are limited, and their mortality rate continues to increase. People with type 2 diabetes have a higher risk of malignant tumors and a higher mortality rate than those without diabetes. Metformin is a commonly used hypoglycemic drug. In recent years, a growing number of studies have indicated that metformin has antitumor effects and increases the sensitivity of malignant tumors to chemotherapy. However, the effect of metformin on different tumors is currently controversial, and the mechanism of metformin's antitumor action is not fully understood. Insights into the effect of metformin on malignant tumors and the possible mechanism may contribute to the development of antitumor drugs.

Effect of Metformin on Breast Density in Overweight/Obese Premenopausal Women.

BACKGROUND: This study investigated the effects of metformin on breast density in overweight/obese premenopausal women. METHODS: Overweight/obese premenopausal women (n=120) were randomly assigned to the metformin or placebo group, and all women received lifestyle interventions. The outcomes included weight, BMI, FPG, FIN, glucose, HOMA-IR, LDL-C, HDL-C, TG, TC, SBP, DBP, FSH, E, AD, and the BIRADS grade, and the incidence of breast cancer was assessed by pathological biopsy and BIRADS grade greater than 4. RESULTS: In total, 120 overweight/obese women completed the 1-year trial. Seven patients had a BIRADS grade greater than 4, including 5 patients who were biopsy positive, in the control group, and 2 patients had a BIRADS grade greater than 4, including 1 patient who was biopsy positive, in the metformin group. Compared with those in the control group, the body weight, BMI, FIN, FPG, HOMA-IR, TC, BIRADS grade and positive pathological biopsy rate in the metformin group were significantly decreased (P<0.05), while AD was significantly increased (P<0.05). The correlation analysis indicated that the BIRADS grade was significantly correlated with weight, BMI, FPG, FIN, HOMA-IR, SBP, AD and the positive pathological biopsy rate, and the positive pathological biopsy rate was significantly correlated with weight, BMI, HOMA-IR, SBP, AD and BIRADS grade. The logistic regression analysis revealed that the BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD and that the positive pathological biopsy rate was significantly correlated with the BIRADS grade. CONCLUSION: As adjunctive therapy, the combination of lifestyle changes and metformin was found to be a safe strategy for improving related metabolic markers and increasing adiponectin. The BIRADS grade was significantly correlated with the positive pathological biopsy rate and AD, and the positive pathological biopsy rate was significantly correlated with the BIRADS grade.

Corrigendum to "EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells".

[This corrects the article DOI: 10.1155/2015/301562.].

Exenatide reduces cardiomyocyte apoptosis by stimulating adiponectin secretion and activating APPL1-AMPK-PPARα axis.

BACKGROUND: To explore the mechanism that exenatide reduces cardiomyocyte apoptosis via the adiponectin pathway in vitro. METHODS: Cardiomyocytes were randomly divided into the control group (group C), diabetic group (group D), diabetic + exenatide treatment group (group DE), diabetic + exenatide treatment + APPL1 overexpression group (group OE), and diabetic + exenatide treatment + APPL1 knock-down group (group KD). After 48 h culture, the apoptosis rate, the adiponectin level in the cell culture fluid, and the expression levels of APPL1, p-AMPK, PPARα and NF-κB were detected by TUNEL, ELISA, and Western blotting, respectively. RESULTS: Compared to group C, the apoptosis rate was markedly increased, the adiponectin level was decreased, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated in group D (P<0.05); in group DE, the apoptosis rate was significantly decreased, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated, as compared with group D (P<0.05). The apoptosis rate in group OE was lower than that in group DE, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated (P<0.05). In group KD, the adiponectin level was elevated and the cardiomyocyte apoptosis rate was increased, as compared to group D (P<0.05). Furthermore, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated compared with group DE (P<0.05). CONCLUSIONS: Exenatide can activate the "APPL1-AMPK-PPARα" anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.

The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered as a risk factor for the progress of liver diseases. After tissue damage, there is the highest amplitude of ubiquitously sterile inflammatory response in the liver, resulting in a major clinical consequence concerning a high prevalence of steatohepatitis in DM patients. This study aimed to investigate the inhibitory efficacy of dapagliflozin (DAPA), a sodium glucose cotransporter-2 (SGLT2) inhibitor, on experimental steatohepatitis with DM. METHODS: DM-steatohepatitis model was established by dual intraperitoneal injection of streptozotocin (STZ) and feeding with the high-fat diet (HFD) in apolipoprotein E-deficient (ApoE-/-) mice (n=40). The mice were concurrently treated with DAPA (1 mg/kg/d) by gavage for 12 weeks. RESULTS: In ApoE-/- mice, dual HFD/STZ dramatically induced hepatic damage and inflammation as compared with HFD alone. DAPA treatment was effective to protect from hepatic damage and inflammation in dual HFD/STZ treated ApoE-/- mice. DAPA also significantly the probability decreased the blood glucose, hepatic lipid accumulation, liver steatosis, and fibrotic response in dual HFD/STZ treated ApoE-/- mice. Further mechanistic investigations indicated that the protection of DAPA on diabetic liver injury was associated with the suppressed production of hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) and the inhibited activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. CONCLUSIONS: These data demonstrate the efficacy of DAPA for protecting liver damage, inflammation and steatosis from experimental steatohepatitis with DM, and indicate a possible involvement of the inhibited activity of ROS-NLRP3 inflammasome.

Lower limb arterial intervention or autologous platelet-rich gel treatment of diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: To investigate whether lower limb vascular intervention or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 82 diabetic LEAD patients with foot ulcers were recruited and divided into three groups: group A (30 patients received basal treatment), group B (21 patients received basal and APG treatment), and group C (31 patients received basal and lower limb vascular intervention treatment). All patients underwent routine follow-up visits for 6 months. The baseline characteristics and parameters were examined. After treatment, changes in all parameters from baseline were recorded. The differences between groups and the relationship among each parameter were determined. RESULTS: There were no differences in the ankle brachial index (ABI) or major amputation between groups A and B (P>0.05). Compared with groups A and B, the ABI and major amputation rate of group C were improved (P<0.05). There were no significant differences in transcutaneous oxygen partial pressure (TcPO2), the heal rate or minor amputation between groups A and C (P>0.05). Compared with groups A and C, TcPO2, the heal rate and minor amputation of group B were improved (P<0.05). The logistic regression analysis indicated that major amputation was mainly associated with the ABI, and minor amputation was mainly associated with TcPO2. Lower limb vascular intervention improves the ABI and reduces major amputation, and APG improves TcPO2 and reduces minor amputation. CONCLUSIONS: In diabetic LEAD patients with foot ulcers, major amputation was mainly associated with the ABI, while minor amputation was mainly associated with TcPO2. Interventional surgery (angioplasty) mainly improves the ABI, reduces the incidence of major amputation and improves the macrovasculature, and APG mainly improves local TcPO2, reduces the incidence of minor amputation and improves the microcirculation.

Increased fractal dimension of left ventricular trabeculations is associated with subclinical diastolic dysfunction in patients with type-2 diabetes mellitus.

The aim of this study was to investigate the relationship among left ventricular (LV) concentric hypertrophy, endocardial remodeling, and myocardial deformation in type-2 diabetes mellitus (T2DM). Fifty-three T2DM patients with normotension and 36 healthy controls underwent cardiovascular magnetic resonance imaging to assess for LV concentric hypertrophy (LV myocardial mass index, LVMMi; LVMMi-to-LV end-diastolic volume index ratio, MVR), endocardial remodeling (fractal dimension of trabeculations, FD), and myocardial deformation (global longitudinal, radial and circumferential strain, systolic and diastolic strain rate). When compared with healthy controls, T2DM was associated with LV concentric hypertrophy (LVMMi: T2DM, 52.7 ± 8.9 g/m2; controls, 48.7 ± 8.4 g/m2, p = 0.032; MVR: T2DM, 0.88 ± 0.19 g/mL; controls, 0.77 ± 0.16 g/mL, p = 0.007), endocardial remodeling (max. apical FD: T2DM, 1.265 ± 0.056; controls, 1.233 ± 0.055, p = 0.008; mean apical FD: T2DM, 1.198 ± 0.043; controls, 1.176 ± 0.043, p = 0.020), and subtle diastolic dysfunction (peak longitudinal diastolic strain rate, PDSRL: T2DM, 1.1 ± 0.2/s; controls, 1.2 ± 0.3/s, p = 0.031). In the stepwise multivariable regression model, the MVR was an independent determinant of the maximum apical FD (standardized ß, sß = 0.525, p < 0.001) and mean apical FD (sß = 0.568, p < 0.001). The mean apical FD was an independent determinant of the PDSRL (p = 0.004). LV concentric hypertrophy is an independent determinant of endocardial remodeling, a process that may contribute to subtle LV diastolic dysfunction in T2DM patients.

Distribution of Microbes and Drug Susceptibility in Patients with Diabetic Foot Infections in Southwest China.

OBJECTIVE: To investigate the microbial distribution and drug susceptibility among diabetic foot ulcers (DFUs) with different Wagner grades and between acute and chronic DFUs. Methods. We enrolled 428 DFU patients who were hospitalized and treated in the Southwest Hospital. We collected deep ulcer secretion for microbial culture and drug susceptibility tests and analyzed the results. We reexamined 67 patients with poor anti-infection efficacy and analyzed microbial species. Results: The 354 positive samples included 201 cases (56.8%) of single-pathogen infections and 153 cases (43.2%) of multiple-pathogen infections before antibiotic therapy. A total of 555 strains were cultivated, including 205 (36.9%) strains of gram-positive organisms (GPOs), 283 (51.0%) gram-negative bacilli (GNB), and 67 (12.1%) fungal strains. In terms of distribution, patients with different Wagner grades had different bacterial composition ratios (P < 0.01). Patients with Wagner grades 3-5 mainly had GNB. The specimens from chronic ulcer wounds were primarily GNB (54.2%), whereas fungi accounted for 14.4% of the infections; the distribution was significantly different from that of acute ulcers (P < 0.01). The susceptibility tests showed that the Staphylococcus genus was more susceptible to vancomycin, linezolid, and tigecycline. Tobramycin was the most effective drug (97%) for the treatment of Escherichia coli, followed by ertapenem (96.4%), imipenem (93.5%), and cefotetan (90%). Most of the remaining GNB were susceptible to antibiotics such as carbapenems, aminoglycosides, fluoroquinolones, ceftazidime, cefepime, and piperacillin-tazobactam (>63.2%). After antibiotic therapy, the positive rate of microbial culture was 52.2%, and the proportion of GNB and fungi increased to 68.9% and 20%. CONCLUSION: The distribution and types of bacteria in diabetic foot infection (DFI) patients varied with the different Wagner classification grades, courses of the ulcers, and antibiotic therapy. Multidrug resistance were increased, and the clinical treatment of DFIs should select the most suitable antibiotics based on the pathogen culture and drug susceptibility test results.

Left atrium passive ejection fraction is the most sensitive index of type 2 diabetes mellitus-related cardiac changes.

The aims of this study were to use cardiovascular magnetic resonance (CMR) cine to assess left atrium (LA) and left ventricle (LV) function and structure in normotensive type 2 diabetes mellitus (T2DM) patients and to identify the most sensitive index of those T2DM-related cardiac changes. Fifty T2DM patients with normotension (25 males, age 54.7 ± 8.7 years, duration of diabetes: 7.5 ± 5.1 years) and 35 controls (16 males, age: 52.2 ± 13.2 years) were prospectively enrolled. All patients were scanned using CMR four- and two-chamber long-axis cine to assess LA and LV structure and function. Normotensive T2DM patients were associated with decreased LA total ejection fraction (EF), passive EF and LV end diastolic volume, normal LA active EF and LV myocardial mass and increased LV mass/volume (M/V). LA total EF and passive EF correlated with body mass index, duration of diabetes and M/V. To differentiate between diabetic patients and healthy controls, area under the receiver operating characteristic (ROC) curve (AUC) values were calculated to be 0.763, 0.706, 0.647 and 0.649 for LA passive EF, total EF, LVEDV and M/V, respectively. The addition of LA total EF, LVEDV, M/V and the combination thereof did not significantly improve AUC values in a model containing LA passive EF. Normotensive T2DM patients were associated with LA decreased total ejection fraction, decreased passive EF and LV concentric remodeling. Among these indices, LA passive EF was the most sensitive to T2DM-related LA function changes.

Dapper1 attenuates hepatic gluconeogenesis and lipogenesis by activating PI3K/Akt signaling.

Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca2+-mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver. It also increased Akt (pAkt) signaling and repressed both gluconeogenesis and lipogenesis. Conversely, Ad-shDapper1-induced knockdown of hepatic Dapper1 promoted gluconeogenesis and lipogenesis. Furthermore, Dapper1 activated PI3K p110α/Akt in an insulin-independent manner by inducing ATP production and secretion in vitro. Blockade of P2 ATP receptors, the downstream phospholipase C (PLC), or the inositol triphosphate receptor (IP3R all reduced the Dapper1-induced increase in cytosolic free calcium and Dapper1-mediated PI3K/Akt activation, as did removal of calcium in the medium. In conclusion, Dapper1 attenuates hepatic gluconeogenesis and lipogenesis in T2D.

Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance.

Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E', A', and E'/A') were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P < 0.05) and no significant difference was in mass at end diastole (P > 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E' (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.

EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells.

Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells.