Dapagliflozin stimulates glucagon secretion at high glucose: experiments and mathematical simulations of human A-cells.

Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations. Because glucagon secretion is regulated by electrical activity we developed a mathematical model of A-cell electrical activity based on published data from human A-cells. With operating SGLT2, simulated glucose application leads to cell depolarization and inactivation of the voltage-gated ion channels carrying the action potential, and hence to reduce action potential height. According to our model, inhibition of SGLT2 reduces glucose-induced depolarization via electrical mechanisms. We suggest that blocking SGLTs partly relieves glucose suppression of glucagon secretion by allowing full-scale action potentials to develop. Based on our simulations we propose that SGLT2 is a glucose sensor and actively contributes to regulation of glucagon levels in humans which has clinical implications

A study of flux lines lattice order and critical current with time of flight small angle neutron scattering

Small angle neutron scattering (SANS) is an historical technique to study the flux lines lattice (FLL) in a superconductor. Structural characteristics of the FLL can be revealed, providing fundamental information for the physics of vortex lattice. However, the spatial resolution is limited and all the correlation lengths of order are difficult to extract with precision. We show here that a time of flight technique reveals the Bragg peak of the FLL, and also its translational order with a better resolution. We discuss the implication of these results for pinning mechanisms in a Niobium sample.Comment: accepted in PR

Ultra-thin titanium nitride films for refractory spectral selectivity

We demonstrate a selectively emitting optical Fabry-P\'erot resonator based on a few-nm-thin continuous metallic titanium nitride film, separated by a dielectric spacer from an optically thick titanium nitride back-reflector, which exhibits excellent stability at 1070 K against chemical degradation, thin-film instabilities and melting point depression. The structure paves the way to the design and fabrication of refractory thermal emitters using the well-established processes known from the field of multilayer and rugate optical filters. We demonstrate that a few-nanometer thick films of titanium nitride can be stable under operation at temperatures exceeding 1070 K. This type of selective emitter provides a means towards near-infrared thermal emission that could potentially be tailored to the accuracy level known from rugate optical filters.Comment: 16 pages, 6 figure

Spin-orbit interaction and the 'metal-insulator' transition observed in two-dimensional hole systems

We present calculations of the spin and phase relaxation rates in GaAs/AlGaAs $p$-type quantum wells. These rates are used to derive the temperature dependence of the weak-localization correction to the conductivity. In $p$-type quantum wells both weak localization and weak anti-localization are present due to the strong spin-orbit interaction. When determining the total conductivity correction one also have to include the term due to hole-hole interaction. The magnitude of the latter depends on the ratio between the thermal energy and the Fermi energy, $k_{\rm B}T/E_{\rm F}$ and whether the system can be considered as ballistic $(k_{\rm B}T \tau_{\rm tr} / \hbar>1)$ or diffusive ($k_{\rm B}T \tau_{\rm tr}/\hbar<1$). We argue that due to the relatively low Fermi energy and the moderate mobilities, in the $p$-type systems in question, the conductivity correction arising from hole-hole interactions is negligible at the highest temperatures accessible in the experiments. Hence the 'metal-insulator' transition observed at these relatively high temperatures could be caused by interference effects. We compare our calculations of the weak anti-localization correction with the experimental results from different independent groups with special emphasis on the experiments by Simmons et al. We find good agreement between predicted and observed transistion density $p_{c}$.Comment: 6 pages, 4 figures. Accepted to PRB (15 June, 2002

Tur\'an Graphs, Stability Number, and Fibonacci Index

The Fibonacci index of a graph is the number of its stable sets. This parameter is widely studied and has applications in chemical graph theory. In this paper, we establish tight upper bounds for the Fibonacci index in terms of the stability number and the order of general graphs and connected graphs. Tur\'an graphs frequently appear in extremal graph theory. We show that Tur\'an graphs and a connected variant of them are also extremal for these particular problems.Comment: 11 pages, 3 figure