title: Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man.
abstract: Mutations in presenilin 1 and 2 are causative factors for early onset familial Alzheimer's disease and possible roles for presenilins include protein trafficking, regulation of apoptosis and/or calcium homeostasis. Presenilin 2 mRNA is expressed in brain, muscle and pancreas but the role of pancreatic presenilin 2 and its relationship to diabetes are unknown. Presenilin 2 immunoreactivity was localised in human and rodent pancreas to islet cells and found in granules of beta-cells. Presenilin 2 was identified in primitive islet and duct cells of human foetal pancreas and in proliferating exocrine duct cells in human pancreatitis but not found in islet amyloid deposits in Type 2 diabetic subjects. Full length, approximately 50 kDa, and the approximately 30 kDa N-terminal fragment of presenilin 2 were identified by western blotting in extracted rodent pancreas but only the 30 kDa fragment was detected in mouse islets and human insulinoma. Post-mortem pancreatic morphology was normal in a subject with the presenilin 2 Met239Val variant and early onset familial Alzheimer's disease. Oral glucose tolerance tests on subjects with the presenilin 2 Met239Val mutation unaffected by early onset familial Alzheimer's disease (mean age 35 years) and on their first-degree relatives without the mutation demonstrated no evidence of glucose intolerance or increased proinsulin secretion. PS2 is a novel &bgr;-cell protein with potential roles in development or protein processing but pancreatic islet structure and function appear to be unaffected by the Met239Val mutation.
authors.affiliation: Diabetes Research Laboratories and Department of Human Anatomy and Genetics, Oxford, UK. emma@drl.ox.ac.uk
authors.forename: E T
authors.initials: ET
authors.lastname: Jaikaran
authors.forename: G
authors.initials: G
authors.lastname: Marcon
authors.forename: L
authors.initials: L
authors.lastname: Levesque
authors.forename: P S
authors.initials: PS
authors.lastname: George-Hyslop
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: A
authors.initials: A
authors.lastname: Clark
mesh_terms: D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D008970:Molecular Weight; D053766:Presenilin-2
chemical_list: D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2