No abstract

Mechanisms of type 2 diabetes mellitus (T2DM) remain elusive, in which obesity (OB) is considered as one of the major risk factors for the disease. A microRNA (miRNA) is a small non-coding RNA molecule functioning in RNA silencing and post-transcriptional regulation of gene expression. It has been demonstrated that some miRNAs can exist in serum stably and is closely related to various diseases. The goal of our study was to identify whether the deregulation of serum miRNAs was associated with T2DM and obesity. Twenty-five subjects with T2DM2, 25 healthy controls, 25 subjects with obesity, and 25 subjects with T2DM combined with obesity were included in the study. A total of 536 miRNA serum samples from these four groups were studied by miRNA polymerase chain reaction (PCR) panels. Data showed that miR-152 and miR-17 were significantly elevated in the OB group, whereas miR-138 was significantly decreased in OB group when compared to controls, T2DM, or T2DM+obesity group. In addition, level of MiR-593 was significantly lower in T2DM group and T2DM+obesity group when compared with controls. Further analysis revealed that the four miRNAs can be used as potential biomarkers to distinguish obesity from T2DM, OB+T2DM, and healthy subjects. Our study is one of the pioneer studies showing the differences in peripheral miRNA level in obesity, T2DM and T2DM combined with obesity. The study results suggest the potential utility of miRNAs in the prediction for obesity and T2DM.

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In recent years, bariatric surgery has emerged as a promising treatment for type 2 diabetes. Bariatric surgery is known to cause alterations in the relative abundance and composition of gut microbiota, which may lead to alterations in the levels of Short-Chain Fatty Acids (SCFAs) that are produced during fermentation by gut microbes. However, little is known about the mechanism of improved glucose metabolism mediated by gut microbiota following bariatric surgery. The aim of our study was to explore whether changes in gut microbiota and in fecal SCFA could be detected following singleanastomosis duodenal jejunal bypass (DJB-sa) surgery, a type of bariatric surgery, and whether these alterations might be related to the improvement of glucose metabolism. To this end, we performed DJB-sa or SHAM surgery on Goto-Kakisaki (GK) rats. We then compared the glucose metabolism as well as changes in gut microbiota and SCFAs levels between both groups. Our results showed that DJB-sa surgery was associated with a significant decrease in fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and fasting serum insulin (FSI). And, DJB-sa led to a change in the composition of gut microbiota including an increase in the relative abundance of SCFA-producing bacteria (Bifidobacterium and Subdoligranulum). Moreover, the levels of six SCFAs in feces, as well as the intestinal expression of SCFA receptors including G-protein-coupled receptor 41 (GPR41), G-protein-coupled receptor 43 (GPR43), and G-protein-coupled receptor 109A (GPR109A), and the expression of Glucagon-like peptide-1 (GLP-1) displayed a significant increase following DJB-sa compared with the Sham group. Thus, the gut microbiota may contribute to the improvement of glucose metabolism in type 2 diabetes following DJB-sa. In conclusion, our study shows that DJB-sa improves glucose metabolism by modulating gut microbiota and by increasing short-chain fatty acid production.

No abstract

Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux-en-Y gastric bypass (RYGB), one of the most common bariatric surgery procedures. We found that the Tfh cells after RYGB were not significantly changed in number, but presented altered cytokine secretion profile, including lower interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-17 secretion. Tfh cells after RYGB also downregulated inducible co-stimulator and programmed death-1. Interestingly, after Tfh cell-naive B cell coculture, Tfh cells after RYGB secreted more IL-10 than autologous Tfh cells before RYGB. The frequencies of IL-10-expressing and transforming growth factor (TGF)-β-expressing regulatory B cells after Tfh cell-naive B cell coculture were directly correlated with the frequency of IL-10-expressing Tfh cells. Depletion of IL-10 in the coculture, however, resulted in fewer regulatory B cells. Finally, patients with greater increase in IL-10-expressing Tfh cells presented further reductions in body mass index, glycaemia, and body fat percentage. Together, these data demonstrated that the Tfh cells after RYGB presented lower inflammatory status and secreted higher IL-10, through which these Tfh cells promoted the development of regulatory B cells. Higher IL-10-expressing Tfh cell level also predicted better patient response to RYGB.

Breast cancer-initiating cells are a relatively radioresistant subpopulation of breast cancer cells. However, the mechanism of this radioresistance is still unclear. This study aimed to investigate the effect of radiation on the levels of signal transducer and activator of transcription 1 (STAT1) in mammospheres of cancer-initiating cells and monolayer cultures of MCF-7 cells. We isolated CD44(+)/CD24(-/low) cancer-initiating cells from MCF-7 cells and propagated them as mammospheres. Next we used realtime quantitative reverse-transcriptase polymerase chain reaction to examine the mRNA level of STAT1 in mammospheres of breast cancer-initiating cells and monolayer cultures of MCF-7 cells. The apoptosis rate and surviving fraction using clonogenic assays was observed after treating the cells with a STAT1 inhibitor. After irradiation, the STAT1 level in the mammospheres was higher than that in the monolayer cultures. STAT1 inhibitor treatment did not cause significant changes in the apoptosis rate and surviving fraction in the MCF-7 monolayer cultures. However, the inhibitor treatment caused significant differences in the apoptosis rate and surviving fraction in mammospheres. Our study provides the first evidence that STAT1 signaling contributes to radioresistance in breast cancer-initiating cells and reveals STAT1 as a promising target to reduce radioresistance and enhance the efficacy of radiotherapy for breast cancer.

Type 2 diabetes (T2D) is a chronic metabolic disorder, which was also found to involve a series of inflammatory disorders, including accumulation of macrophages and T cells in the adipose tissue, increased proinflammatory cytokine production, shifting of macrophage composition toward M1-type, and skewing of peripheral blood T cells toward IL-17 productions. However, these studies were primarily conducted in obese mouse models and/or human subjects with higher BMI, and may not reflect the role of the immune system in non-obese T2D pathogenesis. Here, we examined T cell and monocyte cytokine expression and function in both non-obese and obese T2D patients. We found that IFN-g production by circulating T cells were increased in both non-obese and obese T2D subjects, while IL-17 is only upregulated in obese T2D subjects. Also, circulating monocytes from obese T2D subjects had significantly higher IL-6 production than their counterparts in non-obese T2D subjects. Moreover, monocytes from non-obese T2D subjects could support IFN-g but not IL-17 production in vitro, while that from obese T2D subjects supported both IFN-g and IL-17 production. Together, our results revealed that the role immune system plays in T2D pathogenesis is more complicated than previously thought, and is affected by the person's BMI.