Modeling insuline system

Aspden, T.J., L. Ilium, and O. Skaugrud. 1996. Chitosan as a nasal delivery system Evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models. Eur J Pharm Sci 4 23. 

Vanadium has effects similar to and different from that of insulin [100,101,124], The antidiabetic influence of the metal can be considered insulin-enhancing, rather than insulin-mimetic, because vanadium compounds cannot totally substitute for insulin in any model of diabetes that strictly requires insulin, such as the BB rat [125], a model of type 1 diabetes. In addition, vanadium can exert its antidiabetic effects via a mechanism or combination of mechanisms distinct from that of insulin. The metabolic actions of vanadium on metabolism do not include all of the actions of insulin, yet normal animals produce less serum insulin when given vanadium. The terms insulin-mimetic or insulin-like frequently appear in the literature for actions of vanadium that cannot be classified as similar to or different from that of insulin in the experimental system utilized. 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

Before we can start to develop a model we also have to decide how to interpret the behavior observed in Fig. 2.1. The variations in insulin and glucose concentrations could be generated by a damped oscillatory system that was continuously excited by external perturbations (e.g. through interaction with the pulsatile release of other hormones). However, the variations could also represent a disturbed self-sustained oscillation, or they could be an example of deterministic chaos. Here, it is important to realize that, with a sampling period of 10 min over the considered periods of 20-24 h, the number of data points are insufficient for any statistical analysis to distinguish between the possible modes. We need to make a choice and, in the present case, our choice is to consider the insulin-glucose regulation to operate... 

As the first example, we considered the 2-h to 3-h pulsatile dynamics in insulin secretion rates reported for type II diabetics and age-matched normal persons by Polonsky et al. [18]. A main purpose of that part of our discussion was to emphasize some of the problems involved in defining the structure of the system, i.e. the involved physiological processes. Biological systems have feedback regulations at many different levels and time scales, and the most difficult part of the model formulation is generally to identify the relevant mechanisms. This often involves... 

I. M. Tolic, E. Mosekilde, and ). Sturis Modeling the insulin-glucose feedback system the significance of pulsatile... 

Fig. 5.6 The three model structures for the insulin receptor sub-system. The upper scheme shows a core-model, and the lower scheme a full-scale gray-box model. The center scheme may serve as either model, depending on the circumstances. In any case, translations between all three models are available, and they may be considered...

It is clear, therefore, that core-box models with the additional characteristics of Eq. (11) (such as the insulin model in Section 5.3) have major potential in the future developments of hierarchical models describing larger systems. In this way, the potential drug targets predicted by the core-box model may be judged, not only by their quality tag, but also through their translated importance on the whole-body behavior. Both of these possibilities are very important to achieve the full potential of biosimulation of potential dmg targets. 

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