Ultradian oscillations

Schihler Other oscillators are not affected by the heavy water, such as ultradian oscillators. 

Many hormonal secretion processes also exhibit strong circadian components. This is true, for instance, for cortisol, antidiuretic hormone, and growth hormone. The secretion of growth hormone is markedly increased during the early periods of sleep, and the secretion of antidiuretic hormone also reflects the sleep-wake cycle. The mechanisms underlying these oscillations can often be traced back to cyclical variations in the activity of the central nervous system. At the same time, the circadian rhythm modulates the above-mentioned ultradian oscillations. 

Let us try to illustrate the mechanism-based modeling approach through the process of formulating a model of the ultradian oscillations in human insulin secretion [9], A better understanding of the role and underlying mechanisms of these oscillations is clearly of interest in the design of an optimal treatment of diabetes. 

Fig. 2.1 Examples of ultradian oscillations in human insulin secretion and blood glucose concentration (a) during continuous enteral nutrition and (b) during constant glucose infusion. Closer inspection shows that the glucose oscillations lead the insulin oscillations by a few minutes. Redrawn from [39, 40].

With such independently determined parameters, the model must now be able to reproduce the experimentally observed characteristics of ultradian oscillations in human insulin secretion, e.g. the observed period, the oscillation amplitudes and phase relations, and the ringing of the insulin secretion in response to a meal. If the model can only produce the desired behavior after minor adjustments of the parameters, such adjustments may be performed. In most cases, however, the model either produces temporal variations in qualitative and semi-quantitative agreement with the empirical results or it does not produce anything that resembles them at all. In the latter case we conclude that the model structure is incorrect, and that a new hypothesis must be formulated. 

E. Van Cauter The mechanisms underlying ultradian oscillations of insulin and glucose a computer simulation approach. Am.]. Physiol. 1991, 260 E801-E809. 

C. Simon, G. Brandenberger, and M. Fol-lenius Ultradian oscillations of plasma glucose, insulin and C-peptide in man. J. Clin. Endocrinol. Metab. 1987, 64 669-675. 

The key question pertains of course to the function of PER in the mechanism of the circadian and courtship song rhythms. Through its role(s) in the nervous system of the fly, this protein controls both processes even if these differ in period by some three orders of magnitude. An interesting observation made by Dowse, Hall Ringo (1987) is that a large fraction of mutants that lose circadian rhythmicity still display ultradian oscillations. This raises the possibility that PER may be involved in the production of circadian rhythmicity through the... 

Zeitler, P., G.S. Tannenbaum, D.K.. Clifton R.A. Steiner. 1991. Ultradian oscillations in somatostatin and growth hormone-releasing hormone mRNAs in the brains of adult male rats. Proc. Natl. Acad. Sci. USA 88 8920-4 and Erratum) 89 1997 (1992). 

We conclude that the ultradian insulin oscillations cannot be related to an intermittent supply of glucose. Neither do the oscillations appear to be generated through interaction with counter-regulatory hormones, since analysis of simulta-... 

Fig. 2.2 Simulation of a mechanism-based model of ultradian insulin-glucose oscillations. Using independently determined parameters and nonlinear relations, the model displays self-sustained oscillations of the correct period with proper amplitudes and phase relationships. The model also responds correctly to a meal as well as to changes in the rate of glucose infusion.

Figure 2.2 presents the results obtained with our mechanism-based model of the ultradian insulin-glucose oscillations [9], Although clearly only a preliminary model of the phenomenon, the applied model passes all of the above tests. The model produces self-sustained oscillations of the correct period and proper amplitudes, and the model also responds correctly both to a meal and to changes in the rate of glucose infusion. The next step is to use the model to predict the outcome of experiments that have not previously been performed. To the extent that the model is successful in such predictions, the hypothesis underlying the model structure gains additional support. 

Morre, D. J., Lawler, J., Wang, S., Keenan, T.W., Morre, D.M. 2002. Entrainment in solution of an oscillating NADH oxidase activity from the bovine milk fat globule membrane with a temperature compensated period length suggestive of an ultradian time-keeping (clock) function. Biochim. Biophys. Acta 1559, 10-20. 

High intersex differences and ultradian (period of 6-12 h) oscillations in the activity of catalase were found in the Harderian gland of Syrian hamster, with peak activities in females exceeding those in males by several 100-fold [222]. In oxidative stress response, CAT is phosphorylated at Tyr 231 and Tyr 386 by tyrosine kinases c-Abl and Arg [223]. 

Dowse, H.B. J.M. Ringo. 1993. Is the circadian clock a meta-oscillator Evidence from studies of ultradian rhythms in Drosophila. In Molecular Genetics of Biological Rhythms, M.W. Young, ed. Marcel Dekker, New York, pp. 195-220. 

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