To investigate effects of Sitagliptin on the enhancement of beta-cell function, reducing insulin resistance, serum glucagon like peptide-1 (GLP-1) concentrations and blood glucose in patients with ...type 2 diabetes mellitus (T2D) and suggest one of the underlying mechanisms on beta-cell function and insulin resistance.
This was a cross-sectional and observational study in comparison to the control group. A study population of 44 newly diagnosed patients with T2D treated with Sitagliptin with a dose of 100 mg/day for 3 months was analyzed to compare 52 healthy participants. Indices for beta-cell function, peripheral insulin sensitivity, and insulin resistance were calculated with homeostasis model assessment 2 (HOMA2) calculator and compared. Serum GLP-1 concentrations were analyzed, and regression analysis was conducted to find the correlations between GLP-1 and beta-cell function and insulin resistance.
Newly diagnosed patients with T2D witnessed a significant reduction in beta-cell function, serum GLP-1 concentrations at the time of diagnosis. After treatment with Sitagliptin 100 mg/day, they achieved significant improvements in beta-cell function, peripheral insulin sensitivity and insulin resistance. Serum GLP-1 concentrations were increased significantly to those levels in the control group and correlated with peripheral insulin sensitivity and insulin resistance in patients whose beta-cell functions improved.
Sitagliptin improved beta-cell function, insulin resistance and blood glucose in newly diagnosed patients with T2D. Meanwhile, Sitagliptin ameliorated serum GLP-1 concentrations, which contributed to the enhancement of beta-cell.
We performed a screen for signaling genes by selecting mutant strains of Dictyostelium that fail to develop spores in a pure population but sporulate well in chimerae with wild type cells. We found 9 ...strains whose sporulation was induced up to 10 million-fold in chimerae. Most strains were also able to sporulate in chimerae with each other, but 2 pairs failed to do so, suggesting that the genes in each pair participate in the production of 1 signal. One of the pairs, comD and comB, is described in detail. Sequence analysis revealed that both genes encode putative membrane proteins. ComD is predicted to have 15 transmembrane domains, and ComB has a region of high similarity to the Rab family of small GTPases and 1 transmembrane domain. Similarities between the developmental regulation and cell-type specificity of the genes’ expression, the terminal developmental morphology, and the expression pattern of cell-type specific markers in the mutants suggest that comD and comB participate in 1 signal production pathway. This idea is also supported by a high similarity between the global transcriptional profiles of the mutant strains. Differences between the mutant phenotypes late in development suggest that comD and comB participate in separate processes as well. comD has a cell-autonomous role in the specialization of a novel prespore cell type, whereas comB has a cell-autonomous role in prestalk A cell differentiation.
The projected performance and detector configuration of nEXO are described in this pre-Conceptual Design Report (pCDR). nEXO is a tonne-scale neutrinoless double beta (\(0\nu\beta\beta\)) decay ...search in \(^{136}\)Xe, based on the ultra-low background liquid xenon technology validated by EXO-200. With \(\simeq\) 5000 kg of xenon enriched to 90% in the isotope 136, nEXO has a projected half-life sensitivity of approximately \(10^{28}\) years. This represents an improvement in sensitivity of about two orders of magnitude with respect to current results. Based on the experience gained from EXO-200 and the effectiveness of xenon purification techniques, we expect the background to be dominated by external sources of radiation. The sensitivity increase is, therefore, entirely derived from the increase of active mass in a monolithic and homogeneous detector, along with some technical advances perfected in the course of a dedicated R&D program. Hence the risk which is inherent to the construction of a large, ultra-low background detector is reduced, as the intrinsic radioactive contamination requirements are generally not beyond those demonstrated with the present generation \(0\nu\beta\beta\) decay experiments. Indeed, most of the required materials have been already assayed or reasonable estimates of their properties are at hand. The details described herein represent the base design of the detector configuration as of early 2018. Where potential design improvements are possible, alternatives are discussed. This design for nEXO presents a compelling path towards a next generation search for \(0\nu\beta\beta\), with a substantial possibility to discover physics beyond the Standard Model.
This work summarizes some of our studies of the mechanisms of glucocorticoid action, including aspects of steroid binding to receptors, the activation of glucocorticoid-receptor complexes and the ...regulation of expression of endogenous and transferred glucocorticoid-responsive genes. Studies of the receptor-steroid interaction support the notion that steroid entry is passive. A comparative analysis of binding in isolated cytosol and intact cells suggests that the initial receptor-steroid binding reaction and not subsequent steps such as activation and nuclear binding, is predominantly responsible for the high-affinity state that is generated. The binding is driven by entropy and enthalpy changes at low temperature; at higher temperatures it is driven by entropy changes, with enthalpy working against it. Studies of the activation of the receptor-glucocorticoid complex with the use of highly purified receptors suggest that this step is associated with a change in charge of the receptor-glucocorticoid complex (such as would occur with a dephosphorylation reaction), whereas the data do not support the notion that dissociation of a bound RNA or of receptor oligomers is responsible for generating the nuclear- and DNA-binding activity of the complex. Studies of the regulation by glucocorticoids of expression of the endogenous rat growth hormone (rGH) gene in cultured rat pituitary tumor (GC, GH3D6) cells suggest that glucocorticoids increase the expression of this gene by multiple mechanisms. First, there is a modest direct stimulation of transcription by a mechanism(s) that does not depend on protein synthesis; however, if the cells have been exposed to thyroid hormone for several hours, the steroid exerts a much greater increase in rGH pre-mRNA levels. Secondly, the steroid appears to stimulate some relatively stable function or functions that increase the ability of thyroid hormone to increase rGH levels. Thirdly, the steroid probably increases rGH mRNA stability, since the fold-increases in rGH mRNA exceed those of transcription. Finally, the steroid may, by unknown mechanisms, affect rGH mRNA polyadenylation. The gene transfer experiments utilized the rat and human (h) GH genes and hybrid genes containing either rGH and Herpes Simplex virus thymidine kinase (TK) gene sequences or the human metallothionein-IIA (hMT-IIA) and TK gene sequences. The steroid was found to regulate hMT-IIA gene expression in all glucocorticoid-responsive cell types tested by actions on its 5'-flanking DNA. By contrast, the glucocorticoid regulated GH gene expression in some but not all glucocorticoid-responsive cell types.
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