Fetal pancreatic islets show a deficiency in insulin secretion in response to glucose,
but the underlying mechanism is disputed. By isolating pancreatic islets from 21-day
pregnant rats and culturing them with 2.8 or 11.1 mM glucose for 7 days, we attempted
to clarify the involvement of low glucokinase activity in the poor glucose response
in islets cultured with 2.8 mM glucose relative to the response obtained from those
cultured with 11.1 mM glucose. The insulin secretion induced by 10 mM glyceraldehyde
or 15 mM leucine, but not that induced by 20 mM glucose, from islets cultured with
2.8 mM glucose was higher than the basal insulin secretion, suggesting that the defect
in glucose stimulation in fetal islets may be localized somewhere before the glyceraldehyde
3-phosphate step in the glycolytic pathway. When islets cultured with 11.1 mM glucose
as distinct from those cultured with 2.8 mM glucose were incubated with glucose, the
glycolytic intermediate contents were increased in a concentration- and time-dependent
manner. Utilization of glucose at 20 mM, but not at 5 mM, in islets cultured with
11.1 mM glucose was higher than that in islets cultured with 2.8 mM glucose. The Vmax value of glucokinase, but not that of hexokinase or aldolase, in islets cultured
with 11.1 mM glucose was higher by 150% than that in islets cultured with 2.8 mM glucose.
The results suggest that the poor secretion of insulin in response to glucose can
be explained by insufficient glucose metabolism due to the low glucokinase activity.
Key words
Glucokinase - Fetal Rat Islet - Insulin Secretion - Glycolytic Intermediate - Glucose
Utilization
