5-COMPARTMENT MODEL OF INSULIN KINETICS AND ITS USE TO INVESTIGATE ACTION OF CHLOROQUINE IN NIDDM

Citation
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
Citations number
48
Categorie Soggetti
Physiology
ISSN journal
00029513
Volume
265
Issue
1
Year of publication
1993
Part
1
Pages
50000162 - 50000175
Database
ISI
SICI code
0002-9513(1993)265:1<50000162:5MOIKA>2.0.ZU;2-2
Abstract
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.