Nonlinear Metabolic Dynamics of the Pancreas and Liver

Abstract

Organ level dynamic testing of the metabolic functions of the pancreas and liver have revealed some striking nonlinearities. Glucose provokes a biphasic response in insulin secretion, with dynamic asymmetry and time dependent gain. Amino acid stimulated insulin secretion dynamics contrasted with the dynamic response to glucose in that the gain was not time dependent, and the final phase of insulin secretion did not occur. Also, the magnitude of the amino acid response was very sensitive to the glucose level. A nonlinear model is proposed which accounts for the observed insulin secretory dynamics. The dynamic response of the net glucose balance of the liver in response to glucose was also studied and it was found that, in contrast to the pancreas, the liver can be represented simply by a first order process with a nonlinear static gain curve. These dynamic studies should help explain the nonlinear behavior of the metabolic system at the level of the whole animal.