The important role of FFA in the liver's endogenous supply of glucose is becoming increasingly important. The word metabolic plant refers to the aggregate of all metabolic processes that take place in the body. The pathway is via pyruvic acid and acetyl CaA (see Figure 1). The storage of glycogen is very small in adipose tissue~16) Triglycerides are a more compact form of energy storage.
An increased supply of fatty acids to the liver induces ketogenesis, resulting in the production of ketones - acetone, acetoacetic acid and. A certain amount of glucose is excreted in the urine when the absolute level is greater than 180 mg%. 1 FFA therefore appears to be responsible for the stimulation of gluconeogenesis in the liver during fasting.
A rapid decrease in plasma FFA levels after glucose ingestion would then be expected to result in decreased rates of gluconeogenesis. This ubiquitous hormone is essential for the utilization of glucose in many tissues of the body. Since liver glycogen is not dim-. consumed by more than 50 g. the chosen values for the basal rates of glycogenolysis and gluconeogenesis seem reasonable. ii).
Their conclusions are based on measurements of glucose uptake in the forearm muscles of non-diabetics.
INSULIN CONTROLLER
GLUCAGON CONTROLLER
I PLASMA I
GROWTH HORMONE CONTROLLER
The flow of FFA into and out of this pool is controlled by several hormonal and other factors. In our model, the representations of the processes controlling the movement of FFA into and out of extracellular fluid are assumed to include the transport mechanism across the cell membrane. For example, the endogenous release rate of FFA due to epinephrine is directly related to the plasma concentration of epinephrine.
The role of adipose tissue intracellular FFA in the control of fatty acid storage and release is currently unclear. Much less is known about the exact distribution and state of FFA within the adipocyte. The main assumptions made in building the model are as follows: i) The effects of glucose on adipose tissue are mediated entirely through insulin. ii) Epinephrine and GH are the most predominant lipolytic hormones involved in the short-term responses reported here. iii) Muscle uptake of FFA for immediate oxidation is independent of plasma FFA concentration. iv) Plasma FFA concentration is the stimulus for uptake of FFA by the liver and muscle for storage and uptake of FFA by the liver for production and release of TG and ketones.
Furthermore, the utilization rate of FFA along these pathways is saturation limited at both ends. The fraction of FFA turnover that is immediately oxidized appears to be fairly constant and independent of the plasma FFA level.
FFA MODEL
This subsystem is identified with the portion of the newly synthesized hepatic TG that turns over rapidly. iv). Although it is possible to combine (ii), (iii) and (iv) into a single process (which can be called the FFA utilization sink) without changing any of the simulation results, which we must. The time constants for the two lag elements associated with insulin action were chosen to be the same in all simulation studies.
Rabinowitz et al (49, 5o) provided evidence to support that glucose uptake into adipose tissue (which provides a-glycerophosphate, a necessary precursor for fatty acid esterification) alone cannot explain the rapid fall in plasma FFA. level caused by RV glucose or insulin. ii) Epinephrine: The in vivo effects of epinephrine in humans were studied by Porte et.al. (5l) Dynamics of FFA release. Numerical values for the basal rates of the various exploitation pathways were obtained from a review article by Fritz~17). The basic building blocks used in the construction of the model are shown in Figure 10.
For example, in one of the simulation studies, insulin response to IV insulin was used to estimate the parameter values associated with . insulin degradation. The model reproduced the peak and the time-to-peak quite well, although the difference is somewhat large in the tail part of the response.
ESTIMATION OF PARAMETERS OF THE PROPOOED FFA MODEL
However, by using specific parts of the available data, the parameters associated with specific parts of the model can be identified. The identification problems presented in Section 4.4 assume that the proposed FFA model is a valid representation of the human metabolic control system. The following three experiments proved to be sufficient for estimating the unknown parameters of the FFA model.
It is necessary to first establish the numerical values of the parameters associated with FFA utilization. Since insulin and growth hormone levels are not much affected, we can ignore the terms 6y1, 6y. the right-hand side of Eq. The rest of the parameters of the FFA model are identified in a series of five identification problems discussed in the sequel.
By taking the average of the last two or three measurements, the error in the measure- Our identification procedure makes a good estimate of it (less than 5% error) regardless of the estimated values of and ~p·. Furthermore, by approximately 40 minutes after the start of the infusion there is little difference in the values of p.
One of the issues of particular interest to clinicians is the closed-loop control of metabolic systems. One of the serious problems in implementing the above scheme is the time lag in measuring the glucose concentration. In order to get the same idea about the range of values of the coefficients n.
The prediction scheme described earlier uses glucose data obtained in the interval [o, t - T] where t is the current time and T is the instantaneous delay. The result obtained using the linearly weighted predictive-corrective scheme is shown in Figure 25. The open-loop policy was the same as in the previous result with only prediction and no correction. Models for the metabolism of the above substrates and hormones are briefly discussed here.
It is commonly known as VLDL-TG. • The source of these 2 endogenous TG is the liver. It is cleared by the action of the clearance factor, a substance now known to be the enzyme lipoprotein lipase.
