Mathematical model of metabolism and electrophysiology of amino acid and glucose stimulated insulin secretion: in vitro validation using a beta-cell line

We integrated biological experimental data with mathematical modelling to gain insights into the role played by L-alanine in amino acid-stimulated insulin secretion (AASIS) and in D-glucose-stimulated insulin secretion (GSIS), details important to the understanding of complex β-cell metabolic coupling relationships. We present an ordinary differential equations (ODEs) based simplified kinetic model of core metabolic processes leading to ATP production (glycolysis, TCA cycle, L-alanine-specific reactions, respiratory chain, ATPase and proton leak) and Ca handling (essential channels and pumps in the plasma membrane) in pancreatic β-cells and relate these to insulin secretion. Experimental work was performed using a clonal rat insulin-secreting cell line (BRIN-BD11) to measure the consumption or production of a range of important biochemical parameters (D-glucose, L-alanine, ATP, insulin secretion) and Ca levels. These measurements were then used to validate the theoretical model and fine-tune the parameters. Mathematical modelling was used to predict L-lactate and L-glutamate concentrations following D-glucose and/or L-alanine challenge and Ca levels upon stimulation with a non metabolizable L-alanine analogue. Experimental data and mathematical model simulations combined suggest that L-alanine produces a potent insulinotropic effect via both a stimulatory impact on β-cell metabolism and as a direct result of the membrane depolarization due to Ca influx triggered by L-alanine/Na co-transport. Our simulations indicate that both high intracellular ATP and Ca concentrations are required in order to develop full insulin secretory responses. The model confirmed that K channel independent mechanisms of stimulation of intracellular Ca levels, via generation of mitochondrial coupling messengers, are essential for promotion of the full and sustained insulin secretion response in β-cells

Efeitos da manipulação do estímulo visual e da intenção na oscilação postural de idosas

Este estudo investigou a influência de características do estímulo visual e o efeito da intenção nas respostas do controle postural frente à manipulação visual de adultas idosas. As 20 participantes permaneceram em pé em uma sala móvel durante sete tentativas com duração de 1 minuto cada, olhando para um alvo fixo, medindo-se sua oscilação corporal. Na primeira tentativa não houve qualquer movimento da sala, porém a partir da segunda a sala foi movimentada no sentido ântero-posterior. Para dez participantes, a velocidade de pico da movimentação foi de 0,6 cm/s e, para as demais, de 1,0 cm/s. A partir da quinta tentativa, as participantes foram informadas do movimento da sala e orientadas a resistir à movimentação. Os resultados indicam que a oscilação corporal das idosas é induzida pelo movimento da sala móvel. Intenção e alteração da característica do estímulo visual reduzem a influência da informação visual na oscilação corporal, mas a manipulação de propriedade do estímulo (neste caso, velocidade), é menos efetiva que a intenção. Essa maior dependência da intenção para alterar a influência de um estímulo sensorial no controle postural indica que o funcionamento do sistema de controle postural em idosos não possibilita ajustes "automáticos" de respostas posturais frente a pequenas variações das condições ambientais. Iinformações sobre tais variações podem ser direcionadas de forma a compensar essa diferença.This study examined the influence of both visual stimulus features and intention on postural control responses due to visual manipulation of elderly women. Twenty participants stood upright inside a moving room, for seven trials for 1 min apiece, staring at a fixed target, their body sway being measured. The room was not moved during the first trial, but from the second trial on, it was continuously oscillated back and forward. For ten participants, the moving room oscillated with peak velocity of 0.6 cm/s and for the others, with peak velocity of 1.0 cm/s. From the fifth trial on, participants were informed about the movement of the room and instructed to resist to its influence. Results show that body sway is induced by visual manipulation in elderly adults. Intention and change in visual stimulus lead to less influence of the visual information on body sway, but changes in the stimulus properties (velocity, for that matter), is less effective than intention. This higher dependency on intention for changing sensory influence on postural control suggests that postural control in elderly adults does not benefit from "automatic" postural responses due to small environmental changes. Tips and information about such kind of environmental changes should be used in order to make up for such difference in automatic adjustments observed in the elderly