T-cell factor 7-like 2 (TCF7L2) is an important transcription factor of Wnt/β-catenin signaling, which has critical roles in β-cell survival and regeneration. In preliminary screening assay, we found geniposide, a naturally occurring compound, was able to increase TCF7L2 mRNA level in Min6 cells. Here we aimed to investigate the role of geniposide in β-cell and underlying mechanism involved. Geniposide was found to promote β-cell survival by increasing β-cell proliferation and decreasing β-cell apoptosis in cultured mouse islets after challenge with diabetic stimuli. Geniposide protected β-cell through activating Wnt signaling, enhanced expressions of TCF7L2 and GLP-1R, activated AKT, inhibited GSK3β activity, and promoted β-catenin nuclear translocation. The protective effect of geniposide was remarkably suppressed by siRNAs against β-catenin, or by ICG001 (β-catenin/TCF-mediated transcription inhibitor). Moreover, geniposide promoted β-cell regeneration in vivo to normalize blood glucose in high-fat diet and db/db mice. Increased β-cell proliferation was observed in pancreatic sections of geniposide-treated diabetic mice. Most importantly, geniposide triggered small islet-like cell clusters formation as a result of β-cell neogenesis from ductal epithelium, which was well correlated with the increase in TCF7L2 expression. In exocrine cells isolated from mouse pancreas, geniposide could induce duct cell differentiation through upregulating TCF7L2 expression and activating JAK2/STAT3 pathway. Taken together, we identified a novel role of geniposide in promoting β-cell survival and regeneration by mechanisms involving the activation of β-catenin/TCF7L2 signaling. Our finding highlights the potential value of geniposide as a possible treatment for type 2 diabetes.

Chemokines are a family of small, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with their seven-transmembrane, G protein-coupled receptors. Their major function is the recruitment of leukocytes to inflammation sites, but they also play roles in tumor growth, angiogenesis, organ sclerosis, and autoimmunity. A variety of evidence has accumulated to support the concept that thyroid follicular cells as well as intrathyroidal lymphocytes are able to produce CC and CXC chemokines, which, in turn, promote the initiation and maintenance of an inflammatory process resulting in autoimmune thyroid diseases (AITD). Overexpression of several chemokines in AITD has been demonstrated. Moreover, alterations of CCL2, CCL5, CXCL9, and CXCL10 have been shown in circulation of many patients with AITD. In subjects with Graves' disease, antithyroid drug treatment, radioactive iodine ablation, and thyroidectomy can significantly reduce CXCL10 levels. The measurement of chemokines in serum of AITD patients might provide a useful parameter for the evaluation and prediction of disease activity and progression. Further experimental and clinical studies will expand our understanding of the clinical implications of chemokine detection and the effects of chemokines on the pathogenesis of AITD.

Previously diagnosed diabetes, but not newly diagnosed diabetes or impaired glucose regulation, was associated with a higher prevalence of depression. Patients receiving insulin were more likely to have depression than those not receiving treatment or being treated with oral anti-diabetic medicine.

IBS patients have abnormal local synchronization of spontaneous brain activity in regions involved in visceral afferent processing, emotional arousal, and cognitive modulation. Combining rs-fMRI and ReHo analysis seems to be a valuable approach to investigate the neural basis of IBS.

Compared with a sleep duration of 6-7.9 h, longer sleep duration was associated with a higher prevalence of hypertension and poor glycaemic control in people with diabetes. Moreover, the relationship between sleep duration and prevalent hypertension was U-shaped. These findings may propose important public health implications for diabetes management.

Previously, a new procedure for measuring serum TSH receptor autoantibodies (TRAb) was reported in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 to TSHR-coated ELISA plate wells (TRAb ELISA). The aim of the present study was to evaluate the clinical performance of this assay in comparison to the second generation TRAb assay (TRAb LIA) based on the recombinant human TSH-receptor and chemiluminescence technology (TRAb LIA). Among the 158 patients, 84 patients suffered from Graves' disease (GD), 34 patients had Hashimoto's thyroiditis (HT), and 40 patients had euthyroid nodular thyroid disease (NTD) without signs of autoimmunity. TRAb measurements were performed according to the manufacturer's instructions. Out of 84 GD patients, 80 (95.2%) were TRAb positive as detected by the TRAb LIA. One GD patient had TRAb values within the grey zone (1.0-1.5 IU/l). All patients with HT and NTD were negative except in 6 (8.1%) cases whose TRAb values were within the grey zone. On the basis of the recommended cutoff value (TRAb 1.0 IU/l), the TRAb ELISA found 78 of 84 (92.9%) GD patients to be TRAb positive. None of the patients with HT, but two cases (5.0%) with NTD were TRAb positive. The diagnostic sensitivity of the TRAb LIA and TRAb ELISA assays was 95.2 and 92.9%, while the specificity was 100% and 97.3%, respectively. There was a close correlation (r=0.968, p<0.0001) between both assays in 84 patients with GD. Additionally, the between-run imprecision close to the cutoff limit was assessed. The calculated between-run coefficient of variation (CV) of the TRAb ELISA was 28.2% at the recommended cutoff value of 1.0 IU/l. Due to the evaluated imprecision data we propose a higher cutoff value correlating with a between-run CV of 20% (functional assay sensitivity). Our results indicate that due to a worse imprecision the TRAb ELISA has a slightly lower sensitivity and specificity compared to the TRAb LIA assay. These findings suggest that the M22 monoclonal antibody-based TRAb ELISA is not as reliable as other second generation TRAb assays in the diagnosis of Graves' diseases.

As a result of its spatial confinement in cardiomyocytes, neuronal nitric oxide synthase (nNOS) is thought to regulate mitochondrial and sarcoplasmic reticulum (SR) function by maintaining nitroso-redox balance and Ca2+ cycling. Thus, we hypothesize that ischemic postconditioning (IPostC) protects hearts against ischemic/reperfusion (I/R) injury through an nNOS-mediated pathway. Isolated mouse hearts were subjected to I/R injury in a Langendorff apparatus, H9C2 cells and primary neonatal rat cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, decreased infarct size and improved cardiac function, and the selective nNOS inhibitors abolished these effects. IPostC recovered nNOS activity and arginase expression. IPostC also increased AMP kinase (AMPK) phosphorylation and alleviated oxidative stress, and nNOS and AMPK inhibition abolished these effects. IPostC increased nitrotyrosine production in the cytosol but decreased it in mitochondria. Enhanced phospholamban (PLB) phosphorylation, normalized SR function and decreased Ca2+ overload were observed following the recovery of nNOS activity, and nNOS inhibition abolished these effects. Similar effects of IPostC were demonstrated in cardiomyocytes in vitro. IPostC decreased oxidative stress partially by regulating uncoupled nNOS and the nNOS/AMPK/peroxisome proliferator-activated receptor gamma coactivator 1 alpha/superoxide dismutase axis, and improved SR function through increasing SR Ca2+ load. These results suggest that IPostC protected hearts against I/R injury via an nNOS-mediated pathway.

This study shows the ability of sodium-glucose co-transporter-2 inhibitors to lower atrial natriuretic peptide levels and improve glycaemic control, which may benefit the cardiovascular system.