High-resolution capacitance measurements were used to explore the effects of the gut hormones GLP-1(7-36) amide [glucagon-like peptide I(7-36) amide] and GIP (glucose-dependent insulinotropic polypeptide) on Ca2+-dependent exocytosis in glucagon-secreting rat pancreatic ケ-cells. Both peptides produced a greater than threefold potentiation of secretion evoked by voltage-clamp depolarizations, an effect that was associated with an ∼35% increase of the Ca2+ current. The stimulatory actions of GLP-I(7-36) amide and GIP were mimicked by forskolin and antagonized by the protein kinase A (PKA)- inhibitor Rp-8-Br-cAMPS. The islet hormone somatostatin inhibited the stimulatory action of GLP-I(7-36) amide and GIP via a cyclic AMP–independent mechanism, whereas insulin had no effect on exocytosis. These data suggest that the α-cells are equipped with receptors for GLP-I and GIP and that these peptides, in addition to their well-established insulinotropic capacity, also stimulate glucagon secretion. We propose that the reported inhibitory action of GLP-I on glucagon secretion is accounted for by a paracrine mechanism (e.g., mediated by stimulated release of somatostatin that in turn suppresses exocytosis in the α-cell).
Glucagon-Like Peptide I and Glucose-Dependent Insulinotropic Polypeptide Stimulate Ca2+-Induced Secretion in Rat α-Cells by a Protein Kinase A–Mediated Mechanism
fF, femtofarad; GIP, glucose-dependent insulinotropic polypeptide; GLP-I, glucagon-like peptide I; pC, picocoulomb; PKA, protein kinase A; Rp-8-Br-cAMPS, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate; TEA, tetraethylammonium.
Wei-Guang Ding, Erik Renström, Patrik Rorsman, Karsten Buschard, Jesper Gromada; Glucagon-Like Peptide I and Glucose-Dependent Insulinotropic Polypeptide Stimulate Ca2+-Induced Secretion in Rat α-Cells by a Protein Kinase A–Mediated Mechanism. Diabetes 1 May 1997; 46 (5): 792–800. https://doi.org/10.2337/diab.46.5.792
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