The role of the free cytosolic calcium level in beta-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I(7-37)

• Published in: Endocrinology (Philadelphia) Vol. 132; no. 1; p. 94
• Main Authors: Lu, M, Wheeler, M B, Leng, X H, Boyd, 3rd, A E
• Format: Journal Article
• Language: English
• Published: United States 01.01.1993
• Subjects: Animals; Calcium - metabolism; Cricetinae; Cyclic AMP - metabolism; Cytosol - metabolism; Egtazic Acid - pharmacology; Gastric Inhibitory Polypeptide - pharmacology; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - physiology; Nimodipine - pharmacology; Peptide Fragments; Peptides - pharmacology; Phosphatidylinositols - metabolism; Signal Transduction - physiology; Tumor Cells, Cultured
• ISSN: 0013-7227
• DOI: 10.1210/endo.132.1.8380389

Using the glucose-responsive hamster beta-cell line (hamster insulin tumor cells), we examined the cellular mechanisms by which gastric inhibitory polypeptide (GIP) and glucagon-like peptide I(7-37) (GLP-I) potentiate glucose-stimulated insulin secretion. Glucose alone increased insulin secretion and increased the free cytosolic calcium levels ([Ca2+]i) without altering cAMP content. When added to glucose-stimulated cells, GIP and GLP-I increased cAMP levels and further increased insulin secretion. At 4 mM but not 0.4 mM glucose, both peptides triggered a dose-dependent rise in [Ca2+]i with ED50s of 0.4 and 0.2 nM for GIP and GLP-I, respectively. The increase in [Ca2+]i was blocked by either chelation of extracellular Ca2+ with EGTA or nimodipine, the voltage-dependent Ca2+ channel blocker. Nimodipine also inhibited the potentiation of glucose-stimulated insulin secretion by GIP and GLP-I without inhibition of the stimulatory effect of these two peptides on cAMP accumulation. Neither peptide altered phosphoinositide metabolism, further underlining that the mobilization of intracellular Ca2+ from endoplasmic reticulum is not involved in the GIP and GLP-I signal transduction pathways. This study establishes that GIP and GLP-I potentiate glucose-stimulated insulin secretion by increasing extracellular Ca2+ influx through voltage-dependent Ca2+ channels.