Expression of the adrenomedullin binding protein, complement factor H, in the pancreas and its physiological impact on insulin secretion

Adrenomedullin (AM) is a ubiquitous peptide hormone which, among other func tional roles, reduces insulin secretion in the pancreas. Recently we have d escribed the interaction between AM and the complement regulator protein fa ctor H, which results in mutual modulation of their respective functions. H ere we identify the expression of factor H in the beta cells of the rat pan creatic islets by immunohistochemistry and multiple immunofluorescence foll owed by confocal microscopy. In addition, double immunogold staining under the electron microscope showed coexistence of insulin and factor H immunore activities within the same secretory granules; interestingly, factor H stai ning was found in the electron-lucent haloes whereas the insulin antibody l abeled preferentially the dense cores. The existence of factor H mRNA in th e pancreas was confirmed by RT-PCR and in situ hybridization. The function of factor H in the pancreas was investigated with an insulin secretion assa y. Addition of factor H to freshly isolated islets in the presence of AM re sulted in a further reduction in insulin secretion with a concomitant eleva tion of cAMP, suggesting that factor H increases AM function in glucose hom eostasis. The expression of factor H in the pancreas may play other importa nt roles such as protection against complement-mediated cell lysis.