Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide

Abstract

Amyloid deposits in somatostatinomas are rare observations. To examine the characteristics of this amyloid, we compared amyloid deposits in a somatostatinoma to those found in pancreatic tissue in patients with Type II diabetes mellitus and in insulinomas, using immunohistochemical techniques and specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17 or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II diabetes mellitus and in insulinomas, but not those in the somatostatinoma strongly reacted with these antibodies, or to an antibody to amyloid P component. Amyloid deposits in the somatostatinoma were not reactive with antibodies to somatostatin or to other pancreatic hormones. Electron-microscopic examinations revealed that amyloid fibrils in the somatostatinoma were thinner and more randomly distributed than were those in islets from patients with Type II diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel type of local amyloid in pancreatic islets.Amyloid is a pathologic deposition of polymerized small proteins forming an anti-parallel ß-pleatedsheet conformation (1). There are various types of amyloid, and discrete fibril proteins were noted in case of different diseases. Insular amyloid deposits are common in Type II diabetes mellitus (NIDDM) and in insulinoma (2-5).Somatostatinoma is a rare somatostatin-secreting pancreatic islet cell tumour associated with diabetes mellitus (6-10). About 40 cases of somatostatinoma has been reported since 1979 (6-18), however, amy¬ loid in somatostatinomas has rarely been observed (18). Amyloid deposits in the pancreas from NIDDM patients and in insulinomas were recently seen to consist of islet amyloid polypeptide (IAPP) (2)(3)(4)(5)19,20). This peptide, also termed amylin (21,22), is a 37-amino acid peptide localized in se¬ cretory granules of B-cells in the normal cat pan¬ creas (23) and in the non-diabetic human pancreas (24,25). Analysis of the human IAPP gene (26) and of cDNA encoding IAPP (27,28) suggested that IAPP derives from pancreatic B-cells through proteolytic processing from an 89-amino acid precur¬ sor. However, characteristics of amyloid in soma¬ tostatinomas have not been elucidated.To investigate the characteristics of amyloid in somatostatinomas, we compared the immunoreactivities of amyloid deposits in a somatostatinoma with those in NIDDM pancreatic tissue and insuli¬ nomas, using immunohistochemical techniques and specific antibodies to IAPP and antibodies against other pancreatic hormones or amyloid P component. Fine structures of the amyloid fibrils were also compared electron-microscopically. Patients and Methods Somatostatinoma and insulinomaThe clinical characteristics of one patient with somatosta¬ tinoma and 5 with insulinoma are summarized in Table 1.

Pancreatic Amylin Content in Human Diabetic Subjects and Its Relation to Diabetes

“…On the other hand, a high frequency of amyloid deposits in the islets of diabetic patients has been reported (8,10,(13)(14)(15), and these deposits have been suggested to disrupt the p cell membrane and aggravate the diabetic state (16,17). The present study showed that the pancreatic IRA content was significantly higher in NIDDM patients compared with nondiabetics.…”

“…The tail of the pancreas was minced and the tissue was extracted with formic acid (10). In brief, the tissue was homogenized in 70% formic acid using a Polytron homogenizer, after which the formic acid was evaporated to dryness and the extracts were lyophilized.…”

Overall Sulfation of Heparan Sulfate from Pancreatic Islet β-TC3 Cells Increases Maximal Fibril Formation but Does Not Determine Binding to the Amyloidogenic Peptide Islet Amyloid Polypeptide

“…The mechanism(s) that govern the aggregation of this normally soluble polypeptide are poorly understood. In addition to amyloidogenic IAPP, several other components of islet amyloid have been identified, including apolipoprotein E (5, 6), serum amyloid P component (7), and the heparan sulfate proteoglycan perlecan (6,8).…”

Inhibition of glycosaminoglycan synthesis and protein glycosylation with WAS-406 and azaserine result in reduced islet amyloid formation in vitro

“…These include apolipoprotein E (4), serum amyloid P component (24), and heparan sulfate (HS) proteoglycans (HSPGs) (36), all of which may contribute to hIAPP amyloidogenesis and its related cytotoxicity.…”