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Endocrinology, Vol 133, 1685-1692, Copyright © 1993 by Endocrine Society

ARTICLES

Glucagon-like peptide-1-(7-36)amide and a rise in cyclic adenosine 3',5'-monophosphate increase cytosolic free Ca2+ in rat pancreatic beta- cells by enhancing Ca2+ channel activity

T Yada, K Itoh and M Nakata
Department of Physiology, Kagoshima University School of Medicine, Japan.

Glucagon-like peptide-1 (GLP-1), in the form of either GLP-1-(7- 36)amide or GLP-1-(7-37), has been shown to potently stimulate insulin release in a glucose-dependent manner and is suggested to be a physiological incretin. To explore the mechanisms by which GLP-1-(7- 36)amide stimulates insulin release, we investigated its action on the cytosolic free Ca2+ concentration ([Ca2+]i) in single rat pancreatic beta-cells by the dual wavelength microfluorometry with fura-2. In the presence of 8.3 mM glucose, GLP-1-(7-36)amide at a concentration as low as 3 x 10(-12) M produced a rapid transient increase in [Ca2+]i in some of the single beta-cells. GLP-1-(7-36)amide at 10(-11) M or more evoked the [Ca2+]i response in the majority of beta-cells. In the presence of 2.8 mM glucose, GLP-1-(7-36)amide was without effect. The [Ca2+]i response to GLP-1-(7-36)amide was completely and reversibly inhibited under Ca(2+)-free conditions and by 1 microM nitrendipine, a blocker of L-type Ca2+ channels. Elevation of cAMP in beta-cells by either 10 microM forskolin, an activator of adenylyl cyclase, or 5 mM (bu)2cAMP (db-cAMP) produced an increase in [Ca2+]i similar to that caused by GLP- 1-(7-36)amide. The db-cAMP-induced increase in [Ca2+]i was also completely blocked by nitrendipine. In the continuous presence of GLP-1- (7-36)amide and after the transient [Ca2+]i increase it elicited, db- cAMP failed to evoke the [Ca2+]i response. It is concluded that GLP-1- (7-36)amide at physiological concentrations and a rise in cAMP increase [Ca2+]i in pancreatic beta-cells by enhancing the activity of L-type Ca2+ channels in the beta-cell plasma membrane. It is suggested that the cAMP-operative mechanism is involved in the GLP-1-(7-36)amide action to increase [Ca2+]i in beta-cells.


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