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S B Jørgensen

Publications and source records attributed to S B Jørgensen.

13 recordsLinked to original sources
PubMed2003

A possible role for AMP-activated protein kinase in exercise-induced glucose utilization: insights from humans and transgenic animals.

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism, but the actual signals to glucose transport in response to muscle contraction have not been identified. The 5'-AMP-activated protein kinase (AMPK) has emerged as a putative mediator of contraction-induced glucose transport, although no conclusive evidence has been provided so far. Recent experiments in AMPK transgenic mice suggest that glucose transport induced by 5-amino-4-imidazolecarboxamide riboside (AICAR) or hypoxia is mediated by AMPK. In contrast, contraction-induced glucose transport in rodent skeletal muscle induced by electrical stimulation in vitro or in situ is not influenced or is only partially reduced by abolishing both or one of the catalytic AMPK subunits. This is compatible with exercise studies done in humans, where no tight correlation is found between AMPK activity and glucose uptake during exercise. Taken together, these results question an essential role of AMPK in exercise-induced glucose uptake and imply that one or more additional pathways are involved in mediating glucose transport in skeletal muscle during exercise.

AMP-Activated Protein Kinases↗
PubMed2003

Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models.

AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the alpha1 (AMPK alpha 1(-/-)) and alpha 2 (AMPK alpha 2(-/-)) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPK alpha 1(-/-) mice. On the other hand, AMPK alpha 2(-/-) mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPK alpha 2(-/-) pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPK alpha 2(-/-) mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPK alpha 2(-/-) muscles. Furthermore, AMPK alpha 2(-/-) mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. Increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPK alpha 2(-/-) mice. We suggest that the alpha2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.

AMP-Activated Protein Kinases↗
PubMed2003

Transgenic models--a scientific tool to understand exercise-induced metabolism: the regulatory role of AMPK (5'-AMP-activated protein kinase) in glucose transport and glycogen synthase activity in skeletal muscle.

The AMPK (5'AMP-activated protein kinase) is becoming recognized as a critical regulator of energy metabolism. However, many of these effects in muscle metabolism have been ascribed to AMPK based on the use of the unspecific activator AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside). Using mouse models in which AMPK activity has been specifically blocked (kinase dead) or knocked out we and others have been able to conduct studies gaining more conclusive data on the role of AMPK in muscle metabolism. In this mini-review focus is on AMPK and its regulatory role for glucose transport and GS (glycogen synthase) activity in skeletal muscle, indicating that AMPK is a GS kinase in vivo which might influence GS activity during exercise and that AMPK is involved in AICAR/hypoxia-induced glucose transport but not or only partially in contraction-stimulated glucose transport.

AMP-Activated Protein Kinases↗
PubMed2003

Insulin signalling: effects of prior exercise.

After the discovery and clinical use of insulin for treatment of diabetes it became clear that some of the biological effect of insulin was dependent on the circumstances under which it was given. Relevant for this review is the notion that physical activity, in addition to its own direct metabolic effects also markedly affects the ability of insulin to stimulate a range of metabolic processes. More specifically, during and for a prolonged period after, exercise elicits effects on processes such as insulin-induced muscle glucose uptake and glucose metabolism which influence systemic glucose homeostasis. These phenomena are probably responsible for the improvement in glucose homeostasis and metabolic control that typically occurs with exercise in people with insulin resistance and probably contributes to the reduced risk for development of type 2 diabetes in individuals who engage in regular exercise. Here we focus on the influence of a single bout of exercise on the action of insulin on processes such as glucose uptake and glucose storage in skeletal muscle.

AMP-Activated Protein Kinases↗
PubMed2003

Signalling to glucose transport in skeletal muscle during exercise.

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism. Although the signalling events that increase glucose transport in response to muscle contraction are not fully elucidated, the aim of the present review is to briefly present the current understanding of the molecular signalling mechanisms involved. Glucose uptake may be regulated by Ca++-sensitive contraction-related mechanisms possibly involving protein kinase C, and by mechanisms that reflect the metabolic status of the muscle and may involve the AMP-activated protein kinase. Furthermore the p38 mitogen activated protein kinase may be involved. Still, the picture is incomplete and a substantial part of the exercise/contraction-induced signalling mechanism to glucose transport remains unknown.

AMP-Activated Protein Kinases↗
PubMed2001

A biochemically structured model for Saccharomyces cerevisiae.

A biochemically structured model for the aerobic growth of Saccharomyces cerevisiae on glucose and ethanol is presented. The model focuses on the pyruvate and acetaldehyde branch points where overflow metabolism occurs when the growth changes from oxidative to oxido-reductive. The model is designed to describe the onset of aerobic alcoholic fermentation during steady-state as well as under dynamical conditions, by triggering an increase in the glycolytic flux using a key signalling component which is assumed to be closely related to acetaldehyde. An investigation of the modelled process dynamics in a continuous cultivation revealed multiple steady states in a region of dilution rates around the transition between oxidative and oxido-reductive growth. A bifurcation analysis using the two external variables, the dilution rate, D, and the inlet concentration of glucose, S(f), as parameters, showed that a fold bifurcation occurs close to the critical dilution rate resulting in multiple steady-states. The region of dilution rates within which multiple steady states may occur depends strongly on the substrate feed concentration. Consequently a single steady state may prevail at low feed concentrations, whereas multiple steady states may occur over a relatively wide range of dilution rates at higher feed concentrations.

Aerobiosis↗
PubMed2001

Estimation of kinetic parameters in a structured yeast model using regularisation.

In this work, a procedure for estimating kinetic parameters in biochemically structured models was developed. The approach is applicable when the structure of a kinetic model has been set up and the kinetic parameters should be estimated. The procedure consists of five steps. First, initial values were found in or calculated from literature. Hereafter using sensitivity analysis the most sensitive parameters were identified. In the third step physiological knowledge was combined with the parameter sensitivities to manually tune the most sensitive parameters. In step four, a global optimisation routine was applied for simultaneous estimation of the most sensitive parameters identified during the sensitivity analysis. Regularisation was included in the simultaneous estimation to reduce the effect of insensitive parameters. Finally, confidence intervals for the estimated parameters were calculated. This parameter estimation approach was demonstrated on a biochemically structured yeast model containing 11 reactions and 37 kinetic constants as a case study.

Algorithms↗
PubMed2001

State estimation for a biological phosphorus removal process using an asymptotic observer.

This study investigated the use of an asymptotic observer for state estimation in a continuous biological phosphorus removal process. The estimated states are the concentration of heterotrophic, autotrophic and phosphorus accumulating organisms, polyphosphate, glycogen and PHA. The reaction scheme describing the process was simplified from a combined ASM 1-Delft model. Three examples were investigated: operation at steady state, operation at steady state with a random white-noise in the measurements and operation with a ramp disturbance. In each case, the estimation was quite accurate even if the convergence, driven by the dilution rate, was slow (from 15 to 60 days). The propagation of the measurement noise and a bias in the estimation of glycogen and PHA could be the result of the high condition number of one of the matrices used in the algorithm of the asymptotic observer for the aerated tanks.

Air↗
PubMed1997

Regulation of a continuous yeast bioreactor near the critical dilution rate using a productostat.

Regulation of a continuous bioreactor with Saccharomyces cerevisiae is investigated. A number of different sensors are evaluated for this purpose and the process dynamics is investigated around the critical dilution rate. A sensor for reducing gas concentration in exhaust gases is selected for regulating the substrate flow rate. Closed loop identification experiments are carried out to enable identification of the process dynamics near the critical diluton rate. Due to the time-varying nature of this process an adaptive regulator seems to be a promising tool for providing good regulatory and setpoint tracking performance. A simple third order model is used for a model based control design with a Linear Quadratic (LQ)-regulator. The LQ-regulator performs well experimentally, both in an adaptive version where the model parameters are updated on-line, and in a non-adaptive version. During the test the process is exposed to a large disturbance in substrate feed concentration and to a small setpoint disturbance. The proposed regulator is a practical realisation of a productostat where the product in this case is an undesired primary metabolite. Thus, this paper demonstrates a more general principle of utilizing metabolic overflow metabolism for directing fluxes through a desired metabolic pathway. This principle is applicable in the presented form, if a (by-)product can be measured on-line.

Bioreactors↗
PubMed1997

Continuous cultivation start-up control--an experimental investigation.

A control strategy to avoid development of synchronous growth in carbohydrate limited Saccharomyces cerevisiae cultivations is proposed and experimentally investigated. The basic idea is to control the metabolic flux through the pathways by manipulating the substrate feed rate to keep the ethanol concentration at a low level. An adaptive and a fixed parameter controller were investigated experimentally. Both controllers were initialized at the target conditions for the continuous cultivation, where the uncontrolled process is known to be marginally stable. The latter fact renders it unfeasible to attempt open loop operation at the critical dilution rate. The adaptive controller turned out to be superior to the fixed parameter controller. The superiority of the adaptive controller is ascribed to its ability to identify the process under varying cell activity. The obtained experimental results demonstrate that the desired operating point is reproducibly obtainable. However, after prolonged operation under different types of disturbances the yeast seemed to adapt towards an increased respiratory activity for the same low level of ethanol in the medium.

Algorithms↗
PubMed1970

Contribution of protein to caloric expenditure following injury.

1. There is a common clinical impression that because the nitrogen excretion after injury roughly parallels the increased resting metabolic expenditure and weight loss, the primary source of extra fuel is derived from protein. This study has been undertaken to evaluate the caloric contribution of protein to the daily resting metabolic expenditure (RME). 2. Under the most extreme circumstances of nitrogen excretion, massive soft tissue injury, the caloric contribution of protein is only 20 percent of the RME. Body fat stores are the only other major source of fuel from which the semistarved patient can meet the increased demands for energy. 3. Any form of severe injury impairs the mechanisms by which protein breakdown and nitrogen excretion are reduced. 4. Patients undergoing elective operation in this study did not have a significant rise in RME or nitrogen excretion.

Adolescent↗
PubMedDate not supplied

Evaluation of the potential effects of equalization on the performance of biological phosphorus removal systems.

Experimental data confirming that the phosphorus removal efficiency in biological excess phosphorus removal (BEPR) systems temporarily decreases when the amount of volatile fatty acids (VFAs) added in the anaerobic phase is suddenly increased are presented. This decrease in efficiency results from the fact that acetate uptake is a rapid process and that the phosphate concentration at the end of the anaerobic phase increases rapidly. Because of the nonlinear dependence of the phosphate uptake rate on the poly-beta-hydroxyalkanoate (PHA) content of phosphate-accumulating organisms (PAOs), the increase in PAO PHA content associated with VFA uptake is not able to cause a proportional increase in the rate of phosphate uptake. This causes a temporary imbalance between phosphate release and uptake, leading to lower phosphate removal efficiency. The VFA loading to full-scale BEPR systems is not constant throughout the day, and temporary imbalances such as the ones imposed in the batch tests can occur in full-scale systems. The effect of diurnal variations in loading was demonstrated through simulation of the behavior of an A/OTM system receiving a time-variable influent. Equalization is proposed as a method to diminish the potential for imbalances between phosphate release and uptake by avoiding sudden increases of VFA loading to the plant. Significant improvements in the effluent quality from the simulated system were achieved using equalization. The improvements were greater when the influent contained VFAs than when the VFAs were formed by fermentation in the anaerobic zone. The simulations suggested that it may be possible to decrease the amount of phosphorus discharged by a factor as high as 4 through use of concentration equalization. When both flow and concentration equalization were used, the total amount of phosphorus discharged was decreased by a factor of 8. Equalization can be used, in concert with other strategies for preservation of the PHA content of PAOs under periods of low loadings, to minimize the magnitude of Monday phosphate peaks.

Bacteria, Anaerobic↗