EXISTENCE OF ACTIVIN-A IN A-CELLS AND D-CELLS OF RAT PANCREATIC-ISLET

Activin-A, a member of the transforming growth factor-beta supergene f amily, stimulates insulin secretion in rat pancreatic islets and cause s glycogenolysis in isolated rat hepatocytes. These observations promp ted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observ ed in exocrine pancreas. Cells localized in the mantle of the islets w ere densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-c ells. Furthermore, studies using a double labeling method revealed tha t activin-A coexisted with glucagon in secretory granules in A-cells a nd with somatostatin in D-cells. Antibody against inhibin-A weakly sta ined cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta(A) by a reverse transcription-polymerase c hain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activi n-A on insulin secretion, we examined the effect of activin-A in a flo w-through perifusion system. Activin-A induced a biphasic insulin secr etory response in the presence of 2.8 mm glucose, and a low concentrat ion of activin-A, which does not stimulate insulin secretion by itself , markedly enhanced glucose-mediated insulin secretion at concentratio ns above 2.8 mm glucose. Inhibin-A did not affect insulin secretion. T hese results suggest the existence of activin-A in A- and D-cells of r at pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.