Initiation of insulin secretion in glucose-free medium by activin A.
Activin A is a multifunctional protein known to stimulate insulin secretion (Yasuda H et al., (1993) Endocrinology 133, 624-630). The present 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 response of insulin. In the absence of glucose in perifusate, activin A induced a small but significant release of insulin. The effect of activin A was monophasic in the absence of glucose. In contrast, glucagon-like peptide-1 (GLP-1) had no effect on insulin secretion under the same conditions. However, GLP-1 could enhance insulin secretion induced by activin A in glucose-free medium. Activin A induced a transient increase 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 presence of activin A, however, GLP-1 could induce an elevation of [Ca2+]c. Finally, GLP-1, but not activin A, increased cAMP content in islets incubated in glucose-free medium. These results indicate that activin A, but not GLP-1, induces insulin secretion in glucose-free medium. Activin A is able to reproduce partly the effect of glucose to support the action of GLP-1 in glucose-free medium.
Furukawa
M
M
Department of Cell Biology, Gunma University, Maebashi, Japan.
Nobusawa
R
R
Shibata
H
H
Eto
Y
Y
Kojima
I
I
D028341:Activins; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D003470:Culture Media; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D028341:Activins; D007265:Inhibins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium