Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide.
Body iron is involved in various vital functions. Its uptake in the intestine is regulated by hepcidin, a bioactive peptide originally identified in plasma and urine and subsequently in the liver. In the present study, we provide evidence at the transcriptional and translational levels that hepcidin is also expressed in the pancreas of rat and man. Immunohistochemical studies localized the peptide exclusively to beta-cells of the islets of Langerhans. Immunoelectron microscopical analyses revealed that hepcidin is confined to the insulin-storing beta-cell secretory granules. As demonstrated in insulinoma-derived RINm5F cells, the expression of hepcidin in beta-cells is regulated by iron. Based on the present findings we conclude that pancreatic islets are an additional source of the peptide hepcidin. The localization of this peptide to beta-cells suggests that pancreatic beta-cells may be involved in iron metabolism in addition to their genuine function in blood glucose regulation. In view of the various linked iron/glucose disorders in the pancreas, the present findings may provide an insight into the phenomenology of intriguing mutual relationships between iron and glucose metabolisms.
Kulaksiz
Hasan
H
Division of Gastroenterology, Department of Internal Medicine, University Hospital Ulm, Robert-Koch-Street 8, D-89081 Ulm, Germany.
Fein
Evelyn
E
Redecker
Peter
P
Stremmel
Wolfgang
W
Adler
Guido
G
Cetin
Yalcin
Y
D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D006432:Hemochromatosis / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D007501:Iron