AJP - Endocrinology and Metabolism, Vol 248, Issue 6 681-E686, Copyright © 1985 by American Physiological Society

ARTICLES

A model for augmentation of hepatocyte response to pulsatile glucagon stimuli

D. S. Weigle, D. J. Koerker and C. J. Goodner

We have reported that in the physiological concentration range pulsatile glucagon delivery (6 pulses in 90 min) is a more effective stimulus of rat hepatocyte glucose production than is continuous infusion of the same amount of hormone (pulsatile EC50 = 186 +/- 41 pg/ml, continuous EC50 = 884 +/- 190 pg/ml). At supraphysiological glucagon concentrations, however, the maximal response to continuous glucagon infusion exceeds the response to pulses (241 +/- 14 vs. 140 +/- 11 mumol X G-1 X 90 min-1). In an effort to explain these observations we derived a model for the 90-min hepatocyte responses to pulsatile and continuous glucagon delivery based on the waveform of the hepatocyte response to a transient glucagon stimulus. The model demonstrated that the time constant for response decay was an important determinant of the relative efficacy of the two patterns of hormone delivery. For the observed decay constant value of 0.132 +/- 0.02 min-1 the model predicted the following dose-response parameters: pulsatile EC50 = 131 pg/ml, Rmax = 119 mumol X G-1 X 90 min-1, continuous EC50 = 656 pg/ml, Rmax = 272 mumol X G-1 X 90 min-1. The ability of a model based only on the kinetics of a single pulse to simulate the observed dose-response relationship suggests that pulsatile stimulation is intrinsically more effective than continuous hormonal stimulation.

This article has been cited by other articles:

				P. Genter, N. Berman, M. Jacob, and E. Ipp Counterregulatory hormones oscillate during steady-state hypoglycemia Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E821 - E829. [Abstract] [Full Text] [PDF]