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 functional roles, reduces insulin secretion in the pancreas. Recently we have described the interaction between AM and the complement regulator protein factor H, which results in mutual modulation of their respective functions. Here we identify the expression of factor H in the beta cells of the rat pancreatic islets by immunohistochemistry and multiple immunofluorescence followed by confocal microscopy. In addition, double immunogold staining under the electron microscope showed coexistence of insulin and factor H immunoreactivities within the same secretory granules; interestingly, factor H staining was found in the electron-lucent haloes whereas the insulin antibody labeled preferentially the dense cores. The existence of factor H mRNA in the pancreas was confirmed by RT-PCR and in situ hybridization. The function of factor H in the pancreas was investigated with an insulin secretion assay. Addition of factor H to freshly isolated islets in the presence of AM resulted in a further reduction in insulin secretion with a concomitant elevation of cAMP, suggesting that factor H increases AM function in glucose homeostasis. The expression of factor H in the pancreas may play other important roles such as protection against complement-mediated cell lysis.
Martínez
A
A
Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. martinea@mail.nih.gov
Pío
R
R
López
J
J
Cuttitta
F
F
D053607:Adrenomedullin; D000818:Animals; D018929:Cell Culture Techniques; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007328:Insulin; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D017242:Complement Factor H