Prior exposure of isolated per if used rat islets to the sulfated gut hormone cholecystokinin-8 (CCK-8S) dramatically increased their insulin secretory response to 7.5 mM glucose, 10 mM arginine, and 10 mM α-ketoisocaproate. In the case of glucose, the heightened secretory response was still apparent 60–80 min after CCK-8S removal from the perifusion medium. Prior exposure of perifused islets to arginine (10 mM), tolbutamide (25 μM), or forskolin (1.0 μM) did not sensitize them to 7.5 mM glucose. CCK-8S exposure increased 3H efflux from islets prelabeled with [3H]inositol, and the increase in 3H efflux was sustained after CCK-8S removal from the perifusion medium. The duration of this increase in 3H efflux paralleled the temporal characteristics of this sensitization process and was significantly attenuated by 25 μM asperlicin, a competitive antagonist of CCK binding to its membrane receptor. Arginine, tolbutamide, or forskolin treatment of islets did not increase 3H efflux from [3H]inositol-prelabeled islets. The results suggest that the turnover of membrane phosphoinositides induced by CCK-8S is largely responsible for this heightened state of secretory responsiveness to various stimulants. Secondmessenger molecules generated during phosphoinositide turnover may be responsible for the phenomenon of sensitization displayed by islet tissue to CCK-8S addition.
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December 01 1987
Cholecystokinin-lnduced Alterations in β-Cell Sensitivity: Duration, Specificity, and Involvement of Phosphoinositide Metabolism
Walter S Zawalich;
Walter S Zawalich
Yale University School of Nursing
New Haven, Connecticut
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Victoria A Diaz;
Victoria A Diaz
Yale University School of Nursing
New Haven, Connecticut
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Kathleen C Zawalich
Kathleen C Zawalich
Yale University School of Nursing
New Haven, Connecticut
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Address correspondence and reprint requests to Dr. Walter S. Zawalich, Yale University School of Nursing, 855 Howard Avenue, New Haven, CT 06510.
Diabetes 1987;36(12):1420–1424
Article history
Received:
February 11 1987
Revision Received:
April 21 1987
Accepted:
April 21 1987
PubMed:
2824261
Citation
Walter S Zawalich, Victoria A Diaz, Kathleen C Zawalich; Cholecystokinin-lnduced Alterations in β-Cell Sensitivity: Duration, Specificity, and Involvement of Phosphoinositide Metabolism. Diabetes 1 December 1987; 36 (12): 1420–1424. https://doi.org/10.2337/diab.36.12.1420
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