Immunochemical investigation of insulinomas for islet amyloid polypeptide and insulin: evidence for differential synthesis and storage.
An affinity purified antibody to fragment 14-29 of islet amyloid polypeptide (IAPP) has been prepared. This antibody, which does not cross-react with the related molecule calcitonin gene-related peptide, was used to investigate immunochemically the presence of IAPP in normal and neoplastic human pancreatic endocrine tissue. The pattern of IAPP staining in normal pancreas mirrors that of insulin, although slight differences were observed. In neoplastic tissue, IAPP was found in 16 out of 19 tumours that were positive for insulin, and was absent from one tumour negative for insulin. In some cases there were differences in the staining patterns of IAPP and insulin. These results suggest that the synthesis and secretion of IAPP and insulin are not inter-dependent and support the concept that IAPP has a discrete biological function. Islet amyloid polypeptide was found in six out of six insulinoma amyloid deposits, suggesting that the peptide is an invariable component of these deposits. Over-expression of IAPP, with aberrant processing and/or secretion, may be the causative factor for amyloid deposition in insulinomas and in the islets of type 2 (non-insulin dependent) diabetic patients. Investigation of patients with insulinomas and of insulin cells in culture and tissue sections may help to clarify the biological function of IAPP.
Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, UK.
A J
AJ
Williams
P J
PJ
Coates
D G
DG
Lowe
C
C
McLean
E A
EA
Gale
D007516:Adenoma, Islet Cell / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000032:analysis*; D007340:Insulinoma / Q000737:chemistry* / Q000473:pathology; D058228:Islet Amyloid Polypeptide; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000737:chemistry / Q000473:pathology; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D051381:Rats
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide