Activin A now used as a recombinant product was first isolated from ov
arian fluid. Its effects on insulin and glucagon secretion, Ca-45(2+)
net uptake, Rb-86+ efflux and inositol-trisphosphate (Ins-1,4,5-P3) co
ntent 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 conce
ntration dependent; effects were obvious at 1 and 10 nM activin A. The
effect on insulin release was paralleled by an effect on Ca-45(2+) ne
t uptake. 10 nM activin A were effective in elevating Ins-1,4,5-P3 con
tent at either glucose concentration used. Rb-86+ efflux as an indicat
or for closing K+ channels which leads to a depolarization of the beta
-cell membrane and which is a prerequisite for Ca++ influx was inhibit
ed by activin A at a low glucose concentration (3.0 mM). The data indi
cate that the new peptide activin A elevates insulin release at variou
s glucose concentrations: at low and high glucose concentrations Ca-45
(2+) uptake is involved. At low glucose concentrations inhibition of R
b-86+ efflux is a prerequisite sufficient to lead to a depolarization
and subsequent Ca++ uptake; accumulation of Ins-1,4,5-P3 probably help
s mediating the insulinotropic effect by additionally elevating intrac
ellular Ca++.