Localisation of islet amyloid polypeptide and its carboxy terminal flanking peptide in islets of diabetic man and monkey.
Islet amyloid polypeptide is a normal constituent of islet Beta cells and is derived from a larger precursor by removal of flanking peptides at the carboxy (C) and amino (N) terminals. The role of these flanking peptides in the formation of amyloid in Type 2 (non-insulin-dependent) diabetes mellitus and in insulinomas is unknown. The C-terminal flanking peptide of islet amyloid polypeptide was localised by immunocytochemistry in human and monkey pancreatic islets from Type 2 diabetic and non-diabetic individuals by use of specific polyclonal antisera. Immunoreactivity for the C-terminal peptide was found in insulin-containing cells in both diabetic and non-diabetic tissue: no antibody binding was detected in islet amyloid of Type 2 diabetic man or of monkeys although a positive reaction occurred with antisera for islet amyloid polypeptide. The C-terminal peptide was localised by immunogold electron microscopy in the insulin granules in both diabetic and non-diabetic individuals but, unlike islet amyloid polypeptide, was not detected in lysosomes. The absence of immunoreactivity for the C-terminal peptide in amyloid suggests that incomplete cleavage of this flanking peptide from islet amyloid polypeptide is not a factor in the formation of islet amyloid.
Clark
A
A
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
Lloyd
J
J
Novials
A
A
Hutton
J C
JC
Morris
J F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D006046:Gold; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007150:Immunohistochemistry; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008251:Macaca; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged
D000682:Amyloid; D007106:Immune Sera; D058228:Islet Amyloid Polypeptide; D006046:Gold