Somatostatin inhibition of glucose-, tolbutamide-, theophylline, cytochalasin B-, and calcium-stimulated insulin release in monolayer cultures of rat endocrine pancreas.
Somatostatin inhibited insulin secretion stimulated by glucose, tolbutamide, glucose-theophylline, glucose-cytochalasin B, and calcium in monolayer cell cultures of neonatal rat endocrine pancreas. Both 2-deoxyglucose-inhibited glucose-induced insulin release and basal insulin secretion occurring at glucose 1.7 mM were further reduced by somatostatin. In the presence of somatostatin, 1.0 mug/ml, insulin secretion due to glucose, tolbutamide, or glucose-cytochalasin B were inhibited to levels below the basal secretion seen with glucose 1.7 mM. However, insulin secretion stimulated by calcium, and especially by glucose plus theophylline, remained considerably above basal insulin levels, even with somatostatin 1.0 mug/ml. For all stimuli except calcium, at lower concentrations of somatostatin (0.001-0.10 mug/ml) but not at somatostatin 1.0 mug/ml, increased stimulus concentration partially reversed inhibition by somatostatin. For calcium, even at somatostatin 1.0 mug/ml, insulin release was greater when the calcium concentration was raised. Since net calcium uptake by the beta cell or intracellular translocation of calcium within the beta cell from an organelle-bound pool to a cytoplasmic pool may trigger insulin secretion through interaction of calcium with the microtubular-microfilamentous system, we suggest that the inhibition by somatostatin of calcium influx would explain our findings.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007329:Insulin Antagonists; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*
D007328:Insulin; D007329:Insulin Antagonists; D003571:Cytochalasin B; D013004:Somatostatin; D014044:Tolbutamide; D013806:Theophylline; D005947:Glucose; D002118:Calcium