Activin A: its effects on rat pancreatic islets and the mechanism of action involved.
Activin A now used as a recombinant product was first isolated from ovarian fluid. Its effects on insulin and glucagon secretion, 45Ca2+ net uptake, 86Rb+ efflux and inositol-trisphosphate (Ins-1,4,5-P3) content were investigated in rat pancreatic islets. Activin A increased insulin secretion at either 3.0, 8.3 or 16.7 mM glucose. It decreased glucagon secretion at 3.0, had no effect at 8.3 and increased glucagon secretion at 16.7 mM glucose. The effect on insulin release was concentration dependent; effects were obvious at 1 and 10 nM activin A. The effect on insulin release was paralleled by an effect on 45Ca2+ net uptake. 10 nM activin A were effective in elevating Ins-1,4,5-P3 content at either glucose concentration used. 86Rb+ efflux as an indicator for closing K+ channels which leads to a depolarization of the beta-cell membrane and which is a prerequisite for Ca++ influx was inhibited by activin A at a low glucose concentration (3.0 mM). The data indicate that the new peptide activin A elevates insulin release at various glucose concentrations: at low and high glucose concentrations 45Ca2+ uptake is involved. At low glucose concentrations inhibition of 86Rb+ efflux is a prerequisite sufficient to lead to a depolarization and subsequent Ca++ uptake; accumulation of Ins-1,4,5-P3 probably helps mediating the insulinotropic effect by additionally elevating intracellular Ca++.
Verspohl
E J
EJ
Department of Pharmacology, Institute of Pharmaceutical Sciences, Münster, Germany.
Ammon
H P
HP
Wahl
M A
MA
D028341:Activins; D000704:Analysis of Variance; D000818:Animals; D002132:Calcium Radioisotopes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon / Q000378:metabolism; D066298:In Vitro Techniques; D007265:Inhibins / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes
D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D028341:Activins; D007265:Inhibins; D015544:Inositol 1,4,5-Trisphosphate; D005934:Glucagon; D011188:Potassium