Islet amyloid polypeptide: demonstration of mRNA in human pancreatic islets by in situ hybridization in islets with and without amyloid deposits.

Islet amyloid polypeptide which is normally coexpressed with insulin in beta cells, forms amyloid deposits especially in islets of Type 2 (non-insulin-dependent) diabetic subjects. Occurrence of islet amyloid is paradoxically associated with loss of islet amyloid polypeptide immunoreactivity in beta cells. The present study was undertaken to examine whether the islet amyloid polypeptide gene is expressed in islets with decreased islet amyloid polypeptide immunoreactivity. Pancreatic tissue from 14 patients, 7 with Type 2 diabetes and 7 non-diabetic, were obtained at autopsy or surgery and studied for islet amyloid polypeptide expression by in situ hybridization and for presence of insulin and islet amyloid polypeptide by immunohistochemistry. Six of the specimens from the diabetic and three of those from the non-diabetic patients had varying degrees of islet amyloid polypeptide-derived islet amyloid. Amyloid deposits were associated with decreased numbers of beta cells with islet amyloid polypeptide immunoreactivity despite an apparent normal frequency of insulin-containing cells. This discrepancy might reflect an alteration in islet amyloid polypeptide production or processing at a transcriptional or post-transcriptional level. In contrast to the varying immunohistochemical patterns, islets of all categories showed strong labelling using an islet amyloid polypeptide probe for in situ hybridization. It is concluded that islet amyloid polypeptide production is not altered at the transcriptional level. The following possibilities remain: (1) islet amyloid polypeptide production may be altered at a post-transcriptional level or (2) that islet amyloid polypeptide production is normal but the reduced immunoreactivity of the cells reflects a reduced storage of IAPP in secretory granules.(ABSTRACT TRUNCATED AT 250 WORDS)