Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Abstract

Veterans Administration Hospital, Palo Alto, California 94305 AB S T R A C T Insulin-LuI was administered intravenously to normal subjects, to patients with maturityonset diabetes and normal renal function, and to nondiabetic patients with renal failure. The ensuing plasma disappearance curves of immunoprecipitable radioactive insulin were determined, and these data were analyzed in a variety of ways. Firstly, fractional irreversible loss rates of insulin from plasma were calculated and found to be greatly diminished in patients with renal failure (t4 = 39 min), as compared with normal (t4 = 15 min) and diabetic subjects (ti = 12 min). Secondly, plasma insulin-2'I disappearance curves were resolved into sums of three exponentials by the method of "peeling," and values for the resultant three slopes and half-lives were determined. Patients with normal renal function had similar values for all parameters, while those patients with renal failure were differentiated on the basis of the slope of the last component, with a prolongation of its half-life to 275 min (approximately twice normal). Finally, a three pool model was formulated to describe the kinetics of plasma insulin disappearance in man. representing plasma (pool 1), interstitial fluid (pool 2), and all tissues in which insulin is utilized and degraded (pool 3). The proposed model adequately describing the disappearance curves of insulin-'I observed in all patients indicated that volumes (per cent body weight) of pool 1 (4.04) and pool 2 (10.11), calculated on the basis of the model and the experimental data, corresponded closely to estimates of plasma and interstitial fluid vol- umes obtained by independent means. It also demonstrated that patients with renal failure were characterized by a decreased removal rate of insulin from pool 3 and an increased recycling rate of insulin from pool 3 to pool 2. It is concluded that the proposed model represents a reasonable description of the kinetics of insulin distribution and degradation, and that its use provides quantitative insights into the physiology of insulin metabolism.

Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man.

“…The mean sum of squares derived from the data of all subjects was extremely low for the three-pool model. Moreover, the 72/ 1 ratio, calculated on the basis of the three-pool model and the experimental data, corresponded closely to the previous estimates obtained by a different technique (13). These results provide validation of the proposed model for thyroid hormone kinetics.…”

“…The principal results obtained are presented in Tables I-ITI (13). The results provide further support for the three-pool model.…”

“…The disappearance curves of radioactive thyroid hormones were resolved into three components by the method of peeling (13). The mathematical equation is given by Y = hie-git + h2e-02t + h3e-9t where gX and hX are the slope and the intercept, respectively, of the i"' component and i is either the index 1, 2, or 3.…”

Metabolic clearance rate of radioiodinated human calcitonin in man

“…In this report we discuss the results of studies of calcitonin metabolism in two groups of patients, normal subjects and uremic patients with nonfunctioning kidneys, the latter group being considered of interest in view of the role of the kidneys in the utilization and degradation of polypeptide hormones (2,3). Single injection and constant infusion techniques were used to calculate metabolic clearance rate (MCR) (4).…”

Reasoning about MDPs as Transformers of Probability Distributions

“…Thus, this multimodal behavior can be effectively captured as an MDP. We now describe the compartment model of a specific drug called Insulin− 131 I [16], [17]. Figure 2 shows a labeled state transition diagram of a three compartment model for Insulin− 131 I.…”