Sensitivity analysis of circadian entrainment in the space of phase response curves

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations.Comment: 22 pages, 8 figures. Correction of a mistake in Definition 2.1. arXiv admin note: text overlap with arXiv:1206.414

Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.

Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis

Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling

1939-327X (Electronic) Journal articleObjective : Recent data demonstrate that glucose sensing in different tissues is initiated by an intracellular redox-signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain-glucose hypersensitivity present in obese Zucker rat is related to an alteration in redox signaling. Research design and Methods: Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in ROS levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications of redox state and mitochondrial function were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide dismutase, aconitase activities and mitochondrial respiration. Results : Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated with 1) increased ROS levels in response to this low glucose load, 2) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial level, and 3) over-expression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced-glutathione infusion in the third ventricle fully reversed the cerebral hypersensitivity to glucose. Conclusions : Altogether, these data demonstrate that obese Zucker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an abnormal redox signaling, which originates from mitochondria dysfunction

Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion

Brain Glucagon-Like Peptide-1 Regulates Arterial Blood Flow, Heart Rate, and Insulin Sensitivity

OBJECTIVE— To ascertain the importance and mechanisms underlying the role of brain glucagon-like peptide (GLP)-1 in the control of metabolic and cardiovascular function. GLP-1 is a gut hormone secreted in response to oral glucose absorption that regulates glucose metabolism and cardiovascular function. GLP-1 is also produced in the brain, where its contribution to central regulation of metabolic and cardiovascular homeostasis remains incompletely understood

Airfoil Selection and Wingsail Design for an Autonomous Sailboat

Part of the Advances in Intelligent Systems and Computing book series (AISC, volume 1092)Ocean exploration and monitoring with autonomous platforms can provide researchers and decision makers with valuable data, trends and insights into the largest ecosystem on Earth. Regardless of the recognition of the importance of such platforms in this scenario, their design and development remains an open challenge. In particular, energy efficiency, control and robustness are major concerns with implications in terms of autonomy and sustainability. Wingsails allow autonomous boats to navigate with increased autonomy, due to lower power consumption, and greater robustness, due to simpler control. Within the scope of a project that addresses the design, development and deployment of a rigid wing autonomous sailboat to perform long term missions in the ocean, this paper summarises the general principles for airfoil selection and wingsail design in robotic sailing, and are given some insights on how these aspects influence the autonomous sailboat being developed by the authors.info:eu-repo/semantics/publishedVersio