AJP - Regulatory, Integrative and Comparative Physiology, Vol 247, Issue 3 527-R536, Copyright © 1984 by American Physiological Society
Computer modeling identifies glucokinase as glucose sensor of pancreatic beta-cells
D. Garfinkel, L. Garfinkel, M. D. Meglasson and F. M. Matschinsky
Previous work from this laboratory indicates that glucokinase serves as the
glucose sensor of pancreatic islets. Here we show by nonlinear computer
optimization that the kinetic properties of glucokinase (together with
hexokinase, known to be present in islets) account for the observed
glycolytic rates in islets as a function of glucose level. Alternative
enzymes that have been suggested to perform the same function as
glucokinase, N-acetyl-D-glucosamine kinase and glucose-6-phosphatase, are
shown to have incompatible properties, including a poor fit, different
curve shapes, and unreasonable parameter values resulting from
optimization. Their activities in islets are shown to be too low to account
for observed glucose usage rates. This work endorses our previous proposal
that glucokinase acts as the glucose sensor in pancreatic islet cells.
