THEORETICAL-ANALYSIS OF THE MECHANISMS OF CHRONIC HYPERINSULINEMIA

Steady-state insulin resistance results in a fasting hyperinsulinemia and is a common feature of type II diabetes mellitus and obesity. In t his study, a systems analysis approach was used to study glucose homeo stasis which is considered as the dynamic balance between glucose rele ase by the liver and its uptake by the peripheral tissues as regulated by insulin and glucagon. A series of computer simulation studies were performed utilizing a mathematical model of glucose homeostasis. The purpose of the study was to better understand the factors which contro l glucose balance and to ascertain their relative importance in the de velopment of steady state, fasting hyperinsulinemia. When peripheral c ellular insulin receptors which regulate glucose uptake were reduced t o 25% of normal, the steady state plasma insulin concentration showed little change from the basal level of 8 mu U/ml. When insulin receptor s in the liver were also reduced to 25% of normal, the steady state in sulin concentration increased from the basal levels to 32 mu U/ml. Red ucing pancreatic cu cell insulin receptors to 25% of normal further in creased the hyperinsulinemia to 80 mu U/ml. Hence, this study suggests that the liver and its release of glucose, as controlled by insulin a nd glucagon, plays a central role in the development of a steady-state insulin resistance and hyperinsulinemia. (C) 1997 Elsevier Science Lt d.