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Glycosylphosphatidylinositol‐specific phospholipase D immunoreactivity is present in islet amyloid in type 2 diabetes
Author(s) -
Larson DM,
Kennedy MA,
Bowen RF,
Verchere CB,
Deeg MA
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1600
Subject(s) - islet , amyloid (mycology) , proteoglycan , in vitro , phospholipase d , chemistry , endocrinology , medicine , pancreatic islets , fibril , biochemistry , biology , insulin , extracellular matrix , enzyme , inorganic chemistry
Abstract Numerous apolipoproteins associate with amyloid plaques. A minor high‐density lipoprotein‐associated protein, glycosylphosphatidylinositol‐specific phospholipase D (GPI‐PLD), has recently been described by the authors and others. Since GPI‐PLD is synthesized by, and secreted from, pancreatic islet β cells, the present study examined the hypothesis that GPI‐PLD associates with islet amyloid. GPI‐PLD immunoreactivity was examined in pancreatic tissues from type 2 diabetic and non‐diabetic humans. GPI‐PLD binding to heparan sulphate proteoglycan was determined in the absence or presence of heparan sulphate or heparin. Fibril formation from human islet amyloid polypeptide was determined in the absence or presence of GPI‐PLD. In non‐diabetics, GPI‐PLD immunoreactivity was present and co‐localized with insulin, as opposed to co‐localizing with amyloid in diabetics. No immunoreactivity for apolipoprotein A‐I was present in islet cells or islet amyloid. Heparan sulphate proteoglycan, which is commonly present in most amyloid, bound GPI‐PLD in vitro . GPI‐PLD inhibited the formation of amyloid fibrils from synthetic islet amyloid polypeptide in vitro . GPI‐PLD is therefore present in islet amyloid and appears to derive from local production from islets. This localization likely derives from interaction between GPI‐PLD and heparan sulphate proteoglycan. Since GPI‐PLD also inhibited islet amyloid polypeptide fibril formation in vitro , it is concluded that GPI‐PLD may play a role in islet amyloid formation in type 2 diabetes. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.