Correlation between intestinal flora and GLP-1 receptor agonist dulaglutide in type 2 diabetes mellitus treatment-A preliminary longitudinal study.

GLP-1 receptor agonists (GLP-1 RA) are presently used as the first-line drugs for the clinical treatment of type 2 diabetes mellitus (T2DM). It can regulate blood glucose by stimulating insulin secretion and lowering glucagon levels. We used 16S rRNA amplicon sequencing to detect structural changes in the composition of the intestinal flora of newly diagnosed T2DM after 1 and 48 weeks of dulaglutide administration. Our research found no significant changes in the intestinal flora after the administration of dulaglutide for 1 week to subjects with newly diagnosed T2DM. Nevertheless, after 48 weeks of dulaglutide administration, the composition of the intestinal flora changed significantly, with a significant reduction in the abundance of intestinal flora. Furthermore, we found that fasting glucose levels, fasting c-peptide levels, HbA1c levels, and BMI are also closely associated with intestinal flora. This reveals that intestinal flora may be one of the mechanisms by which dulaglutide treats T2DM.

Relationships of adiponectin to regional adiposity, insulin sensitivity, serum lipids, and inflammatory markers in sedentary and endurance-trained Japanese young women.

Introduction: This study aims to compare the differences in circulating adiponectin levels and their relationships to regional adiposity, insulin resistance, serum lipid, and inflammatory factors in young, healthy Japanese women with different physical activity statuses. Methods: Adipokines (adiponectin and leptin), full serum lipid, and inflammatory factors [white blood cell counts, C-reactive protein, tumor necrosis factor-α, tissue plasminogen activator inhibitor-1 (PAI-1)] were measured in 101 sedentary and 100 endurance-trained healthy Japanese women (aged 18-23 years). Insulin sensitivity was obtained through a quantitative insulin-sensitivity check index (QUICKI). Regional adiposity [trunk fat mass (TFM), lower-body fat mass (LFM), and arm fat mass (AFM)] was evaluated using the dual-energy X-ray absorptiometry method. Results: No significant difference was observed between the sedentary and trained women in terms of adiponectin levels. The LFM-to-TFM ratio and the high-density lipoprotein cholesterol (HDL-C) were the strong positive determinants for adiponectin in both groups. Triglyceride in the sedentary women was closely and negatively associated with adiponectin, as well as PAI-1 in the trained women. The QUICKI level was higher in the trained than sedentary women. However, no significant correlation between adiponectin and insulin sensitivity was detected in both groups. Furthermore, LFM was associated with a favorable lipid profile against cardiovascular diseases (CVDs) in the whole study cohort, but this association became insignificant when adiponectin was taken into account. Conclusions: These findings suggest that adiponectin is primarily associated with regional adiposity and HDL-C regardless of insulin sensitivity and physical activity status in young, healthy women. The associations among adiponectin, lipid, and inflammatory factors are likely different in women with different physical activity statuses. The correlation of LFM and a favorable lipid profile against CVD and adiponectin is likely involved in this association.

Exenatide improves hepatocyte insulin resistance induced by different regional adipose tissue.

Obesity is resulted from energy surplus and is characterized by abnormal adipose tissue accumulation and/or distribution. Adipokines secreted by different regional adipose tissue can induce changes in key proteins of the insulin signaling pathway in hepatocytes and result in impaired hepatic glucose metabolism. This study aimed to investigate whether exenatide affects key proteins of IRS2/PI3K/Akt2 signaling pathway in hepatocytes altered by the different regional fat depots. Six non-obese patients without endocrine diseases were selected as the research subjects. Their subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)were co-cultured with HepG2 cells in the transwell chamber. In the presence or absence of exenatide, adipokines content in the supernatant of each experimental group was detected by ELISA. In addition, HepG2 cells in each co-culture group with and without insulin were collected, and the expression of key proteins IRS2, p-IRS2(S731), PI3K-p85, Akt2, and p-Akt2(S473) was detected by western blotting (WB). The results showed that the adipokines IL-8, MCP-1, VEGF, and sTNFR2 in the supernatant of HepG2 cells induced by different regional adipose tissue were significantly higher than those in the HepG2 group, and VAT released more adipokines than SAT. Furthermore, these adipokines were significantly inhibited by exenatide. Importantly, the different regional fat depot affects the IRS2/PI3K/Akt2 insulin signaling pathway of hepatocytes. Exenatide can up-regulate the expression of hepatocyte proteins IRS2, PI3K-p85, p-Akt2(S731) inhibited by adipose tissue, and down-regulate the expression of hepatocyte proteins p-IRS2(S731) promoted by adipose tissue. The effect of VAT on the expression of these key proteins in hepatocytes is more significant than that of SAT. But there was no statistical difference in the expression of Akt2 protein among each experimental group, suggesting that exenatide has no influence on the expression of Akt2 protein in hepatocytes. In conclusion, exenatide may improve hepatic insulin resistance (IR) by inhibiting adipokines and regulating the expression of key proteins in the IRS2/PI3K/Akt2 pathway.

Genome-Wide Identification of the Physic Nut WUSCHEL-Related Homeobox Gene Family and Functional Analysis of the Abiotic Stress Responsive Gene JcWOX5.

Plant-specific WOX transcription factors have important regulatory functions in plant development and response to abiotic stress. However, the identification and functional analysis of members of the WOX family have rarely been reported in the physic nut plant until now. Our research identified 12 WOX genes (JcWOXs) in physic nut, and these genes were divided into three groups corresponding to the ancient clade, WUS clade, and intermediate clade. Expression analysis based on RNA-seq and qRT-PCR showed that most of the JcWOX genes were expressed in at least one of the tissues tested, whereas five genes were identified as being highly responsive to drought and salt stresses. Subcellular localization analysis in Arabidopsis protoplast cells showed that JcWOX5 encoded a nuclear-localized protein. JcWOX5-overexpression plants increased sensitivity to drought stress, and transgenic plants suggested a lower proline content and CAT activity, higher relative electrolyte leakage, higher MDA content, and higher rate of water loss under drought conditions. Expression of some stress-related genes was obviously lower in the transformed rice lines as compared to their expression in wild-type rice lines under drought stress. Further data on JcWOX5-overexpressing plants reducing drought tolerance verified the potential role of JcWOX genes in responsive to abiotic stress. Collectively, the study provides a foundation for further functional analysis of JcWOX genes and the improvement of physic nut crops.

Genome-wide analysis of Jatropha curcas MADS-box gene family and functional characterization of the JcMADS40 gene in transgenic rice.

BACKGROUND: Physic nut (Jatropha curcas), an inedible oilseed plant, is among the most promising alternative energy sources because of its high oil content, rapid growth and extensive adaptability. Proteins encoded by MADS-box family genes are important transcription factors participated in regulating plant growth, seed development and responses to abiotic stress. However, there has been no in-depth research on the MADS-box genes and their roles in physic nut. RESULTS: In our study, 63 MADS-box genes (JcMADSs) were identified in the physic nut genome, and classed into five groups (MIKCC, Mα, Mß, Mγ, MIKC*) according to phylogenetic comparison with Arabidopsis homologs. Expression profile analysis based on RNA-seq suggested that many JcMADS genes had the strongest expression in seeds, and seven of them responded in leaves to at least one abiotic stressor (drought and/or salinity) at one or more time points. Transient expression analysis and a transactivation assay indicated that JcMADS40 is a nucleus-localized transcriptional activator. Plants overexpressing JcMADS40 did not show altered plant growth, but the overexpressing plants did exhibit reductions in grain size, grain length, grain width, 1000-seed weight and yield per plant. Further data on the reduced grain size in JcMADS40-overexpressing plants supported the putative role of JcMADS genes in seed development. CONCLUSIONS: This study will be useful in order to further understand the process of MADS-box genes involved in regulating growth and development in addition to their functions in abiotic stress resistance, and will eventually provide a theoretical basis for the functional investigation and the exploitation of candidate genes for the molecular improvement of physic nut.

[Association study of apolipoprotein e gene polymorphism and cerebral infarction in type 2 diabetic patients].

In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,epsilon(2)epsilon(3),epsilon(3)epsilon(3) as well as epsilon(3)epsilon(4) was no significant difference in three groups (epsilon(2)epsilon(3) : 13.2%,epsilon(3)epsilon(3) : 67.6%,epsilon(3)epsilon(4) : 16.2%in CON group;epsilon(2)epsilon(3) : 19.4%,epsilon(3)epsilon(3): : 70.1%epsilon(3)epsilon(4) : 9%in T2DM group;epsilon(2)epsilon(3) : 15.2%,epsilon(3)epsilon(3) : 75%,epsilon(3)epsilon(4) : 4.2%in T2DMCI group). The allele frequencies of epsilon(2),epsilon(3) and epsilon(4) were not significantly different in the three groups, either(epsilon(2) : 9.6%,epsilon(3) : 82.4%,epsilon(4) : 8.1%in CON group; epsilon(2) :10.5%,epsilon(3) :84.3%,epsilon(4) : 5.2%in T2DM group; epsilon(2) :11.8%,epsilon(3) :84.7%,epsilon(4) : 3.5%in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.