The effect of high glucose on insulin resistance and mitochondrial calcium homeostasis.

<p>A: The effect of 33mM glucose (HG) on Akt phosphorylation was performed by western blotting method. B&C: The effect of HG on mitochondrial calcium was assessed using the adenoviruses expressing the low-affinity mitochondrial probe. D&G: The effect of HG on cytosolic calcium was evaluated by adenoviruses expressing the cytosolic probe. Data are shown as a mean ± SEM of at least three separate experiment. NG: normal glucose, HG: high glucose, # <0.05, * <0.01, NS = not significance.</p

The effect of MCU inhibition on the phosphorylation of MAPK and NF-κB pathway.

<p>HepG2 cells were treated with HG for 24 h. After treatment, cells were lysed and protein extracts were immunoblotted with specific antibodies. The effect of MCU inhibition on JNK (A), P38 (B), ERK (C) and IKKα-β (D) phosphorylation has been demonstrated. Data are shown as a mean ± SEM of at least three separate experiment. MCU knockdown cells, SC: Scramble, NG: normal glucose, HG: high glucose, # <0.05, * <0.01, * * <0.001.</p

The effect of MCU inhibition on ROS production in HepG2 cells.

<p>HepG2 cells were treated with HG for 24 h. A: H₂O₂ levels were measured using flow cytometry with DCFH-DA. B: Mitochondrial ROS level using MitoSOX red dye. Data are shown as a mean ± SEM of at least three separate experiment.: MCU knockdown cells, SC: Scramble, NG: normal glucose, HG: high glucose, # <0.05, * <0.01, * * <0.001.</p

Importance of MCU inhibition in high glucose-induced pro-inflammatory and coagulative responses.

<p>HepG2 stable cells were generated by infecting the cells with the supernatants of lentiviruses expressing MCU shRNA. Real-time PCR and western blotting were used to detect MCU mRNA and protein levels in HepG2 stable cells, respectively. A: Protein levels of MCU, B: mRNA level of MCU, C) mitochondrial calcium concentration in MCU-KD cells. D: the effect of MCU inhibition on the mRNA expression of TNF-α (E), IL-6 (F), PAI-1 (G), FGA (H), and FGB(I) were measured using real time PCR. Data are shown as a mean ± SEM of at least three separate experiment. MCU-KD: MCU knockdown cells, SC: Scramble, NG: normal glucose, HG: high glucose, # <0.05, * <0.01, * * <0.001.</p

Association of circulating CTRP9 with soluble adhesion molecules and inflammatory markers in patients with type 2 diabetes mellitus and coronary artery disease

<div><p>C1q/TNF-related protein 9 (CTRP9) is a paralogue of adiponectin with known favorable effects on lipid and glucose metabolism. A potential role of CTRP9 for regulation of endothelium function has been suggested by previous studies. However, no studies have examined the relation between serum CTRP9 levels and adhesion molecules in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The present study was conducted on 337 subjects who underwent coronary angiography and were categorized into four groups according to the presence of CAD and T2DM (control, CAD, T2DM and CAD+T2DM). Serum levels of CTRP9, adiponectin, sICAM-1, sVCAM-1, sE-Selectin, IL-6 and TNF-α were measured. It was found that the circulating CTRP9 levels were independently associated with increased risk of CAD and T2DM in addition to elevated levels of serum CTRP9 in CAD, T2DM and CAD+T2DM groups. A significant association of serum CTRP9 levels with adhesion molecules in CAD and T2DM patients as well as serum TNF-α levels in CAD individuals was noted. A significant relation between the circulating levels of CTRP9 and HOMA-IR in T2DM subjects was also observed. The results revealed increased circulating levels of CTRP9 in T2DM and CAD individuals which suggests a compensatory response to insulin resistance, inflammatory milieu and endothelial dysfunction; however, more studies are needed to confirm this.</p></div

Clinical and biochemical characteristics of study population.

<p>Clinical and biochemical characteristics of study population.</p

Pearson correlation of CTRP9 with anthropometric and metabolic parameters.

<p>Pearson correlation of CTRP9 with anthropometric and metabolic parameters.</p

Odds ratios for development of CAD, T2DM and CAD+T2DM based on serumCTRP9 levels.

<p>Odds ratios for development of CAD, T2DM and CAD+T2DM based on serumCTRP9 levels.</p

Serum levels of CTRP9 in control, CAD, T2DM and CAD+T2DM category.

<p>a) Serum CTRP9 levels were lower in controls (148.7 ± 4.0) than CAD (202.0 ± 4.9), T2DM (191.4 ± 10.1) and CAD+T2DM (211.2 ± 6.8). (all, p<0.001). b) Serum concentration of CTRP9 was higher in women (208.8 ± 6.2) compared to men (181.8 ± 3.7) (p<0.001).</p