title: Differential expression of vacuolar-type H+-ATPase between normal human pancreatic islet B-cells and insulinoma cells.
abstract: Recent studies have shown that bafilomycin A(1)-sensitive vacuolar type H+-ATPase (V-ATPase) is responsible for the acidification of intracellular compartments in eukaryotic cells. B-cells of pancreatic islets also are known to include acidifying secretory vesicles which are the major cellular site of proinsulin to insulin conversion. This study was designed to examine immunohistochemically the level of V-ATPase protein expression in normal pancreas (five cases) and benign insulinoma (six cases), using mouse monoclonal antibody raised against the 116 kDa subunit of human V-ATPase. Light microscopic immunohistochemistry revealed that moderate to marked V-ATPase expression was observed in normal islet B-cells, while insulinoma cells in each case expressed V-ATPase faintly or not at all. By immunoelectron microscopy, the majority of secretory vesicles in insulinoma cells did not express V-ATPase protein at their endomembranes, although mild to marked V-ATPase expression was noted at the endomembrane of secretory vesicles in normal islet B-cells. Thus, differential expression of V-ATPase protein at the endomembrane of secretory vesicles was observed between normal islet B-cells and insulinoma cells. These findings suggest that the reduced activity of V-ATPase per insulin secretory vesicle in insulinoma cells have a profound effect on the efficiency of proteolytic cleavage of proinsulin.
authors.affiliation: KANAZAWA UNIV,SCH MED,DEPT ANAT,KANAZAWA,ISHIKAWA 920,JAPAN. KANAZAWA UNIV,SCH MED,DEPT INTERNAL MED,KANAZAWA,ISHIKAWA 920,JAPAN. KANAZAWA UNIV,FAC PHARMACEUT SCI,DEPT BIOCHEM,KANAZAWA,ISHIKAWA 920,JAPAN. TOTTORI UNIV,FAC MED,DEPT PATHOL,YONAGO,TOTTORI 683,JAPAN.
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Numata
authors.forename: S
authors.initials: S
authors.lastname: Iseki
authors.forename: H
authors.initials: H
authors.lastname: Kitagawa
authors.forename: M
authors.initials: M
authors.lastname: Kayahara
authors.forename: T
authors.initials: T
authors.lastname: Nagakawa
authors.forename: K
authors.initials: K
authors.lastname: Miwa
authors.forename: A
authors.initials: A
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Morise
authors.forename: S
authors.initials: S
authors.lastname: Ohkuma
authors.forename: T
authors.initials: T
authors.lastname: Terada