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Journal of Cell Science, Vol 112, Issue 13 2137-2144, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man

ET Jaikaran, G Marcon, L Levesque, PS George-Hyslop, PE Fraser and A Clark
Diabetes Research Laboratories and Department of Human Anatomy and Genetics, Oxford, UK. emma@drl.ox.ac.uk

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.


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© The Company of Biologists Ltd 1999