title: The subcellular distribution of cyclin-D1 and cyclin-D3 within human islet cells varies according to the status of the pancreas donor.
abstract: OBJECTIVE
  In humans, the rate of beta cell proliferation declines rapidly during the postnatal period and remains low throughout adult life. Recent studies suggest that this may reflect the distribution of cell cycle regulators which, unusually, are located in the cytosolic compartment of beta cells in islets isolated from adults. In the present work, we examined whether the localisation of cyclin-D molecules is also cytosolic in the islet cells of pancreatic samples studied in situ.
  
  
  METHODS
  Immunohistochemical approaches were employed to examine the subcellular localisation of cyclin-D1, -D2 and -D3 in human pancreatic samples recovered either from heart-beating donors or post mortem. Immunofluorescence methods were used to reveal the cellular localisation of cyclin-D1 and -D3.
  
  
  RESULTS
  The distribution of cyclin-D2 was invariably cytosolic in islet cells, whereas the localisation of cyclin-D1 and -D3 varied according to the status of the donor. In pancreatic sections from heart-beating donors these molecules were primarily nuclear. By contrast, in samples collected post mortem, they were mainly cytosolic. Cyclin-D1 was detected only in beta cells whereas cyclin-D3 was detected in both alpha and beta cells. The proportion of donors who were immunopositive for cyclin-D1 declined from 71% in controls to 30% in those with type 1 diabetes. Cyclin-D3 was present in the islets of the majority of donors in both groups.
  
  
  CONCLUSIONS
  The subcellular localisation of cyclin-D molecules varies according to the status of the donor. Both cyclin-D1 and -D3 can be found in the nuclei of human islet cells in situ.
authors.affiliation: Institute of Biomedical & Clinical Science, University of Exeter Medical School, RILD Building, Barrack Road, Exeter, EX2 5DW, UK.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Mark A
authors.initials: MA
authors.lastname: Russell
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Richardson
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000378:metabolism*; D056742:Cyclin D2 / Q000378:metabolism; D056743:Cyclin D3 / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D014019:Tissue Donors; D055815:Young Adult
chemical_list: C530104:CCND1 protein, human; C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D019938:Cyclin D1