[Effect of cholecystokinin and secretin on insulin binding to rat pancreatic acini and pancreatic cancer cell line AR42J cells].
In order to clarify the interaction of hormones which exert various effects on the exocrine pancreas, we investigated the effect of cholecystokinin (CCK) and secretin on subsequent insulin binding to pancreatic acini and cultured AR42J cells derived from azaserine-induced acinar cell carcinoma of the pancreas. CCK at concentrations of 100pM-10nM inhibited subsequent 125I-insulin binding to pancreatic acini. 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited 125I-insulin binding whereas A23187 had little effect, suggesting that the inhibitory effect of CCK is mediated by protein kinase C. On the other hand, 100pM-10nM secretin had no effect on subsequent 125I-insulin binding to pancreatic acini, although higher concentrations of forskolin and 8 bromoadenosine 3', 5'-cyclic monophosphate inhibited 125I-insulin binding. In addition, secretin exerted no potentiating effect on the inhibitory effect of CCK on 125I-insulin binding to pancreatic acini. Based on these results, we further investigated the effect of CCK and TPA on subsequent 125I-insulin binding to AR42J cells. In this carcinoma cell line, inhibitory effect of CCK and TPA on insulin binding was completely abolished. The present results suggest, therefore, that hormonal interaction may play an important role in the regulation of exocrine pancreatic function including acinar cell growth.
Second Department of Internal Medicine, Kobe University School of Medicine.
Y
Y
Okabayashi
M
M
Koide
H
H
Hasegawa
T
T
Okutani
Y
Y
Kido
K
K
Matsushita
M
M
Otsuki
M
M
Kasuga
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012633:Secretin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007328:Insulin; D012633:Secretin; D002766:Cholecystokinin