Switching from neutral protamine Hagedorn insulin to insulin glargine 300?U/mL improves glycaemic control and reduces hypoglycaemia risk : results of a multicentre, prospective, observational study

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p<0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p<0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p<0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight

AKT1S1 (AKT1 substrate 1 (proline-rich))

Review on AKT1S1, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Adipocyte-derived factors impair insulin signaling in differentiated human vascular smooth muscle cells via the upregulation of miR-143

AbstractCardiovascular complications are common in patients with type 2 diabetes. Adipokines have been implicated in the induction of proliferative and pro-atherogenic alterations in human vascular smooth muscle cells (hVSMC). Other reports demonstrated the importance of the miRNA cluster miR-143/145 in the regulation of VSMC homeostasis and insulin sensitivity. Here we investigated whether the detrimental effects of adipokines on hVSMC function could be ascribed to alterations in miR-143/145 expression. The exposure of hVSMC to conditioned media (CM) from primary human subcutaneous adipocytes increased the expression of smooth muscle α-actin (SMA), and the miR-143/145 cluster, but markedly impaired the insulin-mediated phosphorylation of Akt and its substrate endothelial nitric oxide synthase (eNOS). Furthermore, CM promoted the phosphorylation of SMAD2 and p38, which have both been linked to miR-143/145 induction. Accordingly, the induction of miR-143/145 as well as the inhibition of insulin-mediated Akt- and eNOS-phosphorylation was prevented when hVSMC were treated with pharmacological inhibitors for Alk-4/5/7 and p38 before the addition of CM. The transfection of hVSMC with precursor miR-143, but not with precursor miR-145, resulted in impaired insulin-mediated phosphorylation of Akt and eNOS. This inhibition of insulin signaling by CM and miR-143 is associated with a reduction in the expression of the oxysterol-binding protein-related protein 8 (ORP8). Finally, the knock-down of ORP8 resulted in impaired insulin-mediated phosphorylation of Akt in hVSMC. Thus, the detrimental effects of adipocyte-derived conditioned media on insulin action in primary hVSMC can be ascribed to the Alk- and p38-dependent induction of miR-143 and subsequent downregulation of ORP8

A broad-band FT-ICR Penning trap system for KATRIN

The KArlsruhe TRItium Neutrino experiment KATRIN aims at improving the upper limit of the mass of the electron antineutrino to about 0.2 eV (90% c.l.) by investigating the beta-decay of tritium gas molecules T(2) -> ((3)HeT)(+) + e(-) + (nu) over bar (e). The experiment is currently under construction to start first data taking in 2012. One source of systematic uncertainties in the KATRIN experiment is the formation of ion clusters when tritium decays and decay products interact with residual tritium molecules. It is essential to monitor the abundances of these clusters since they have different final state energies than tritium ions. For this purpose, a prototype of a cylindrical Penning trap has been constructed and tested at the Max-Planck-Institute for Nuclear Physics in Heidelberg, which will be installed in the KATRIN beam line. This system employs the technique of Fourier-Transform Ion-Cyclotron-Resonance in order to measure the abundances of the different stored ion species.The two Penning traps have been financed by the BMBF (grant to the University of Karlsruhe) under project codes 05CK5VKA/5 and 05A08VK2. The support of the Deutsche Forschungsgemeinschaft for the development of the FT-ICR detection technique for precision mass spectrometry under contract number BL981-2-1 is gratefully acknowledged. We thank A. Gotsova for her help during tests in Mainz and Prof. C. Weinheimer for useful discussions related to this project. We warmly thank the LPC trappers group for providing the attenuation grids. D. Rodríguez is a Juan de la Cierva fellow and acknowledges support from the Spanish Ministry of Science and Innovation through the José Castillejo program to provide funding for a 5-month stay at the MPI-K. Sz. Nagy acknowledges support from the Alliance Program of the Helmholtz Association EMMI. S. Lukic acknowledges support by the Transregional Collaborative Research Centre No. 27 “Neutrinos and Beyond”, funded by Deutsche Forschungsgemeinschaft

Position-sensitive ion detection in precision Penning trap mass spectrometry

A commercial, position-sensitive ion detector was used for the first time for the time-of-flight ion-cyclotron resonance detection technique in Penning trap mass spectrometry. In this work, the characteristics of the detector and its implementation in a Penning trap mass spectrometer will be presented. In addition, simulations and experimental studies concerning the observation of ions ejected from a Penning trap are described. This will allow for a precise monitoring of the state of ion motion in the trap.Comment: 20 pages, 13 figure

The magic nature of 132Sn explored through the single-particle states of 133Sn

Atomic nuclei have a shell structure where nuclei with 'magic numbers' of neutrons and protons are analogous to the noble gases in atomic physics. Only ten nuclei with the standard magic numbers of both neutrons and protons have so far been observed. The nuclear shell model is founded on the precept that neutrons and protons can move as independent particles in orbitals with discrete quantum numbers, subject to a mean field generated by all the other nucleons. Knowledge of the properties of single-particle states outside nuclear shell closures in exotic nuclei is important for a fundamental understanding of nuclear structure and nucleosynthesis (for example the r-process, which is responsible for the production of about half of the heavy elements). However, as a result of their short lifetimes, there is a paucity of knowledge about the nature of single-particle states outside exotic doubly magic nuclei. Here we measure the single-particle character of the levels in 133Sn that lie outside the double shell closure present at the short-lived nucleus 132Sn. We use an inverse kinematics technique that involves the transfer of a single nucleon to the nucleus. The purity of the measured single-particle states clearly illustrates the magic nature of 132Sn.Comment: 19 pages, 5 figures and 4 table

TRIGA-SPEC: A setup for mass spectrometry and laser spectroscopy at the research reactor TRIGA Mainz

The research reactor TRIGA Mainz is an ideal facility to provide neutron-rich nuclides with production rates sufficiently large for mass spectrometric and laser spectroscopic studies. Within the TRIGA-SPEC project, a Penning trap as well as a beam line for collinear laser spectroscopy are being installed. Several new developments will ensure high sensitivity of the trap setup enabling mass measurements even on a single ion. Besides neutron-rich fission products produced in the reactor, also heavy nuclides such as 235-U or 252-Cf can be investigated for the first time with an off-line ion source. The data provided by the mass measurements will be of interest for astrophysical calculations on the rapid neutron-capture process as well as for tests of mass models in the heavy-mass region. The laser spectroscopic measurements will yield model-independent information on nuclear ground-state properties such as nuclear moments and charge radii of neutron-rich nuclei of refractory elements far from stability. This publication describes the experimental setup as well as its present status.Comment: 20 pages, 17 figure