Role of Sclerostin in the Bone Loss of Postmenopausal Chinese Women with Type 2 Diabetes

Objective To evaluate the role of sclerostin in bone loss of postmenopausal Chinese women with type 2 diabetes me｜litus. Methods The postmenopausal patients suffering from type 2 diabetes mellitus and age, body mass index, and duration of menopause matched healthy controls were enrolled into this cross-sectional study according to criteria of inclusion and exclusion.

Linoleic Acid Activates GPR40/FFA1 and Phospholipase C to Increase [Ca^(2+)]_i Release and Insulin Secretion in Islet Beta-Cells

Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.

Metabolomics of Fuzi-Gancao in CCl4 induced acute liver injury and its regulatory effect on bile acid profile in rats

BACKGROUND Fuzi(Radix aconiti lateralis)-Gancao(Radix glycyrrhizae)is one of the most classical drug pairs of traditional Chinese medicine.In clinical practice,decoctions containing Fuzi-Gancao(F-G)are often used in the treatment of liver diseases such as hepatitis and liver failure.AIM To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile.METHODS The pharmacodynamic effect of F-G on CCl4 induced acute liver injury in rats was evaluated,and an ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver.RESULTS Twenty-four differential metabolites were identified in serum samples.The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group.Subsequently,a UPLC-MS/MS method for simultaneous determination of 11 bile acids,including cholic acid,ursodeoxycholic acid,glycochenodeoxycholic acid,glycochenodeoxycholic acid,taurocholic acid,glycocholic acid,chenodeoxycholic acid,deoxycholic acid,taurochenodeoxycholic acid,taurocholic acid,and glycinic acid,was established to analyze the regulatory mechanism of F-G in serum.F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group.CONCLUSION F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine,and reducing the accumulation of free bile acids in the liver.F-G could also regulate the compensatory degree of taurine,decreasing the content of taurine-conjugated bile acids to protect hepatocytes.

Nucleotide-binding Oligomerization Domain-1 Ligand Induces Inflammation and Attenuates Glucose Uptake in Human Adipocytes

Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 （NOD1） on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand （all P〈0.01）. Insulin-induced glucose uptake was decreased upon the activation of NOD1 （P〈0.05）. NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake （all P〈0.05）. Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.

Narrowband perfect terahertz absorber based on polar-dielectrics metasurface

We theoretically propose a narrowband perfect absorber metasurface(PAMS) based on surface phonon polaritons in the terahertz range. The PAMS has unit cell consisting of a silver biarc on the top, a thin polar-dielectric in the middle and a silver layer at the bottom. The phonon polaritons are excited at the interface between the silver biarc and the polar dielectric, and enhance the absorption of the PAMS. The absorption peak is at 36.813 μm and the full width half maximum(FWHM) is nearly 36 nm, independent of the polarization and incidence angle. The electric fields are located at the split of the biarc silver layer and the quality factor Q is 1150. The FWHM decreases with the decreasing split width. When the thickness of the bottom layer is larger than 50 nm, the narrow band and high absorption are insensitive to the thickness of those layers. The designed absorber may have useful applications in terahertz spectra such as energy harvesting, thermal emitter, and sensing.

Saturated Fatty Acid Induces Insulin Resistance Partially Through Nucleotide-binding Oligomerization Domain 1 Signaling Pathway in Adipocytes

Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 （NOD1）, a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB （NF-κB） activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[SH] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD 1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-R, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD 1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.