Fast Traveling-Wave Reactor of the Channel Type

The main aim of this paper is to solve the technological problems of the TWR based on the technical concept described in our priority of invention reference, which makes it impossible, in particular, for the fuel claddings damaging doses of fast neutrons to excess the ~200 dpa limit. Thus the essence of the technical concept is to provide a given neutron flux at the fuel claddings by setting the appropriate speed of the fuel motion relative to the nuclear burning wave. The basic design of the fast uranium-plutonium nuclear traveling-wave reactor with a softened neutron spectrum is developed, which solves the problem of the radiation resistance of the fuel claddings material.Comment: 18 pages, 5 figures, 2 table

Geometrical methods in loop calculations and the three-point function

A geometrical way to calculate N-point Feynman diagrams is reviewed. As an example, the dimensionally-regulated three-point function is considered, including all orders of its epsilon-expansion. Analytical continuation to other regions of the kinematical variables is discussed.Comment: 6 pages, LaTeX, 3 eps figures, contribution to proceedings of ACAT2005 (Zeuthen, May 2005

Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production

© 2018 The Author(s). Published by Elsevier Inc.Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.Peer reviewe

Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells

© The Author(s) 2018Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.Peer reviewedFinal Published versio

Molecular determinants and intracellular targets of taurine signalling in pancreatic islet β‐cells

AbstractAimDespite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet β‐cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into β‐cells and its acute and chronic intracellular interactions.MethodsThe molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 β‐cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2–20 mM), using the hormone release and imaging of intracellular signals as surrogate read‐outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals.ResultsTaurine transporter TauT was expressed in the islet β‐cells, with the transport of taurine and homologs having a weak sulfonate specificity but significant sensitivity to the molecular weight of the transporter. Taurine, hypotaurine, homotaurine, and β‐alanine enhanced insulin secretion in a glucose‐dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic β‐cell insulinotropic effects of taurine were highly sensitive to co‐agonism with GLP‐1, forskolin, tolbutamide, and membrane depolarization, with an unanticipated indifference to the activation of PKC and CCK8 receptors. Pre‐culturing with GLP‐1 or KATP channel inhibitors sensitized or, respectively, desensitized β‐cells to the acute taurine stimulus.ConclusionTogether, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and β‐cell function, consistent with the antidiabetic potential of its dietary low‐dose supplementation