GLP-I(7-36) amide augments Ba2+ current through L-type Ca2+ channel of rat pancreatic beta-cell in a cAMP-dependent manner

The whole-cell patch-clamp method was used to examine the effect of glucagon-like peptide I (GLP-I)(7-36) amide on the activation process of L-type Ca2+ channels of rat pancreatic beta-cells. After depolarization, GLP-I (1-100 nmol/l) caused action potentials in cells exposed to a glucose-free solution for 10 min, The percentage of cells producing action potential depended on the concentration of GLP-I, In some cells, GLP-I caused action potentials without the prior depolarization of the membrane, In cells exposed to the glucose-free solution for longer than 30 min, or in cells that were deprived of ATP by a means of the conventional whole-cell configuration, GLP-I (20 nmol/l) did not cause the electrical excitation, Application of GLP-I augmented the maximum Ba2+ current (I-Ba) through L-type Ca2+ channels and shifted the current voltage curve to the left. Values of changes in the maximum I-Ba depended on GLP-I concentration, Application of dibutyryl cAMP (dbcAMP, 1 mmol/l) also augmented I-Ba. In cells pretreated with Rp-cAMP, dbcAMP did not change the magnitude of I-Ba. Also in cells pretreated with Rp-cAMP, GLP-I failed to augment I-Ba. These results suggest that in pancreatic beta-cells, GLP-I, by a cAMP-dependent mechanism, increases opening of L-type Ca2+ channels, cAMP-dependent augmentation of Ca2+ entry as well as cAMP production itself by GLP-I plays a crucial role in controlling insulin secretion.