Glucagon-Like Peptide I and Glucose-Dependent Insulinotropic Polypeptide Stimulate Ca2+-Induced Secretion in Rat α-Cells by a Protein Kinase A–Mediated Mechanism

• DOI: 10.2337/diab.46.5.792
• Publication Date: 2013-09-19T17:42:54Z
• Authors: Wei-Guang Ding; Erik Renström; Patrik Rorsman; Karsten Buschard; Jesper Gromada
• Keywords: 0303 health sciences; Glucagon-Like Peptides; Gastric Inhibitory Polypeptide; Glucagon; Cyclic AMP-Dependent Protein Kinases; Exocytosis; Peptide Fragments; Rats; Islets of Langerhans; 03 medical and health sciences; Glucagon-Like Peptide 1; Animals; Calcium; Calcium Channels; Somatostatin

High-resolution capacitance measurements were used to explore the effects of gut hormones GLP-I(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 alpha-cells. Both peptides produced a greater than threefold potentiation secretion evoked by voltage-clamp depolarizations, an effect that was associated with approximately 35% increase Ca2+ current. The stimulatory actions mimicked forskolin antagonized protein kinase A (PKA)-inhibitor Rp-8-Br-cAMPS. islet hormone somatostatin inhibited action via cyclic AMP-independent mechanism, whereas insulin had no exocytosis. These data suggest alpha-cells are equipped receptors for GLP-I these peptides, addition their well-established capacity, also stimulate glucagon secretion. We propose reported inhibitory is accounted paracrine mechanism (e.g., mediated stimulated release turn suppresses alpha-cell).