Defective regulation of glucokinase in rat pancreatic islet cell tumours.
The role of glucokinase in the regulation of insulin secretion was examined in normal rat pancreatic islets and in chemically- and radiation-induced rat pancreatic B-cell tumours which show an impaired insulin secretory response to glucose. In normal rats glucokinase activity in cytoplasmic fractions of pancreatic islets was decreased with the duration of fasting and increased by refeeding or insulin administration. This observation is consistent with the induction of glucokinase by insulin. Hexokinase activity was only slightly reduced during fasting. Glucokinase activity decreased in cytoplasmic fractions of streptozotocin-nicotinamide-induced rat pancreatic islet cell tumours. Glucokinase activity contributed about 75% to the total glucose phosphorylation capacity in cytoplasmic fractions of normal pancreatic islets and of small (less than 1 mg) streptozotocin-nicotinamide-tumours. This proportion decreased to about 20% in the large streptozotocin-nicotinamide tumours. Glucokinase activity in cytoplasmic fractions of transplantable radiation-induced NEDH (New England Deaconess Hospital) rat B-cell tumours was seven times lower than in normal pancreatic islets and contributed only 15% to the total glucose phosphorylation capacity. In contrast, hexokinase activity of the NEDH tumour B-cells was 2.5 times higher than normal. Decreased glucokinase activity in the chemically- and radiation-induced tumour B-cells appears to result from a loss of the ability of insulin to induce this enzyme and may explain the lack of insulin secretory responsiveness of these tumour B-cells.
Lenzen
S
S
Tiedge
M
M
Flatt
P R
PR
Bailey
C J
CJ
Panten
U
U
D007516:Adenoma, Islet Cell / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D005215:Fasting; D005941:Glucokinase / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D006593:Hexokinase; D005941:Glucokinase