Localization of Activin A/EDF in the Normal and Diabetic Rat Pancreas: Immunohistochemical and In Situ Hybridization Studies

We examined the immunohistochemical localization of activin A/erythroid differentiation factor (EDF) in the pancreases of normal and diabetic rats with insulin-dependent diabetes mellitus or noninsulin-dependent diabetes mellitus to elucidate how activin A/EDF modulates insulin secretion. In both the normal and the diabetic pancreas, all of the cells staining with antirecombinant human (rh) activin A/EDF antiserum were insulin-producing B-cells, and they gradually decreased in number with the development of diabetic changes in both types of diabetic rats. No rh activin A/EDF immunoreactivity was detected in A-, D-, or pancreatic polypeptide (PP) cells in the islets, or in the exocrine cells. Thein situ hybridization (ISH) method showed that activin A/EDF mRNA is localized in activin A/EDF-positive cells. These data indicated that activin A/EDF localizes in insulin-producing B-cells of normal and diabetic pancreases, and may act as an autocrine modulator of insulin secretion.