R. Hovorka et al., 5-COMPARTMENT MODEL OF INSULIN KINETICS AND ITS USE TO INVESTIGATE ACTION OF CHLOROQUINE IN NIDDM, The American journal of physiology, 265(1), 1993, pp. 50000162-50000175
We have constructed a five-compartment model of insulin kinetics. The
model structure was chosen to reflect insulin distribution in systemic
plasma, hepatic plasma, and interstitial fluid and insulin binding to
the liver and peripheral receptors, and it included receptor-mediated
and non-receptor-mediated insulin degradation. Model parameters were
estimated from plasma insulin concentrations measured during hyperinsu
linemic euglycemic clamp studies. In the fasting condition, the model-
derived mean residence time of endogenously secreted insulin was 71 mi
n, of which 62 min were spent bound to the liver receptor, 6 min bound
to the peripheral receptor, 2 min circulating in hepatic or systemic
plasma, and 1 min in the interstitial fluid. More than 80% of total in
sulin was bound to the liver receptor, indicating that the liver is by
far the largest insulin reservoir. The model was employed to assess t
he effect of chloroquine on insulin kinetics in patients with non-insu
lin-dependent diabetes mellitus (NIDDM). Chloroquine significantly alt
ered parameter vector. However, the mean residence times of insulin in
the system and in the periphery were not affected, indicating that th
e beneficial effect of chloroquine in patients with NIDDM under condit
ions of euglycemia could not be attributed to changes in insulin kinet
ics.