Immaturity of glucose-induced insulin secretion in fetal rat islets is due to low glucokinase activity.
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.
Taniguchi
S
S
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Tanigawa
K
K
Miwa
I
I
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005985:Glyceraldehyde; D005941:Glucokinase; D007930:Leucine; D005947:Glucose