The role of the free cytosolic calcium level in beta-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I(7-37)
| Autor: | Xing-Hong Leng, Michael B. Wheeler, Ming Lu, A. E. Boyd |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
endocrine system
medicine.medical_specialty medicine.medical_treatment Glucagon-Like Peptides Gastric Inhibitory Polypeptide Biology Phosphatidylinositols Glucagon Islets of Langerhans chemistry.chemical_compound Cytosol Endocrinology Gastric inhibitory polypeptide Glucagon-Like Peptide 1 Cricetinae Internal medicine Insulin Secretion Cyclic AMP Tumor Cells Cultured medicine Extracellular Animals Insulin Egtazic Acid Endoplasmic reticulum Peptide Fragments EGTA chemistry Calcium Nimodipine Signal transduction Beta cell Peptides hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Endocrinology. 132:94-100 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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