INITIATION OF INSULIN-SECRETION IN GLUCOSE-FREE MEDIUM BY ACTIVIN-A

Activin A is a multifunctional protein known to stimulate insulin secr etion (Yasuda H et al., (1993) Endocrinology 133, 624-630). The presen t study was conducted to determine whether activin A augments insulin secretion in the absence of ambient glucose. In the presence of 2.7 mM glucose, and 1.25 mM calcium, activin A induced a biphasic secretory reponse of insulin. In the absence of glucose in perifusate, activin A induced a small but significant release of insulin. The effect of act ivin A was monophasic in the absence of glucose. In contrast, glucagon -like peptide-1 (GLP-1) had no effect on insulin secretion under the s ame conditions. However, GLP-1 could enhance insulin secretion induced by activin A in glucose-free medium. Activin A induced a transient in crease in cytoplasmic-free calcium concentration, [Ca2+](c), in a fura -2-loaded islet superfused with glucose-free buffer. Again, GLP-1 was without effect on [Ca2+](c) by itself in glucose-free buffer. In the p resence of activin A, however, GLP-1 could induce an elevation of [Ca2 +](c). Finally, GLP-1, but not activin A, increased cAMP content in is lets incubated in glucose-free medium. These results indicate that act ivin A, but not GLP-1, induces insulin secretion in glucose-free mediu m. Activin A is able to reproduce partly the effect of glucose to supp ort the action of GLP-1 in glucose-free medium.