The stimulus-secretion coupling of glucose-induced insulin release. XLVII. The possible role of calmodulin.
Pancreatic islets contain calmodulin. This protein activates adenylate cyclase in a subcellular fraction of rat islets in a calcium-dependent fashion. The Km for calmodulin was close to 0.1 microM, well below the concentration of endogenous calmodulin. Trifluoperazine and the trifluoromethylphenothiazine derivative of domperidone inhibited glucose-stimulated insulin release without affecting glucose oxidation by the islets. When insulin release was inhibited by 30% or more, this inhibition coincided with a reduction in the 45Ca net uptake by the islets. Both drugs suppressed the increment in adenylate cyclase activity evoked by calmodulin in a particulate fraction derived from the islets. However, the drugs also decreased basal and NaF-stimulated adenylate cyclase activities. Within limits, these data are compatible with the participation of endogenous calmodulin in the normal process of insulin release.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D004294:Domperidone / Q000031:analogs & derivatives*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology
D001562:Benzimidazoles; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D007328:Insulin; D010640:Phenothiazines; C028899:domperidone trifluoromethylphenothiazine; D014268:Trifluoperazine; D004294:Domperidone; D000262:Adenylyl Cyclases; D005947:Glucose; D002118:Calcium