Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.

Abstract

Amyloid deposits localized to the islets of Langerhans are typical of non-insulin-dependent human diabetes mellitus and of diabetes mellitus in adult cats. Amyloid deposits also commonly occur in insulin-producing pancreatic tumors. We have purified a major protein-insulinoma or islet amyloid polypeptide (IAPP)-from human and cat islet amyloid and from amyloid of a human insulinoma. IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da. The amino acid sequence is unique but has >40% identity with the human calcitonin gelie-related peptide. A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions. An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells.

Ganglioside‐induced amyloid formation by human islet amyloid polypeptide in lipid rafts

“…Native human islet amyloid polypeptide (hIAPP) is the primary component of the amyloid deposits [6,7] found in the pancreatic islet of patients with type 2 DM [8,9]. The causal relationship between the formation of amyloid fibrils containing hIAPP and the onset of type 2 DM has not been resolved.…”

Effects of beta cell granule components on human islet amyloid polypeptide fibril formation

“…Islet amyloid polypeptide (IAPP) is a 37 amino acid residue polypeptide, mainly expressed in fl-cells [1]. It is in human a product of a 69 amino acid precursor by cleavage at double basic amino acid residues [2][3][4].…”

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

“…On the other hand, IAPP has been shown to hyperpolarise beta-cell membranes [25], an effect that could protect beta cells from exhaustion when demands for insulin secretion are high, such as in peripheral insulin resistance. It should also be borne in mind that IAPP has a neuropeptide-like structure; the sequence of IAPP shares about 50 % identity with that of CGRPs; [5,6], the most ubiquitously expressed neuropeptides in primary sensory neurons. Here, IAPP is expressed in a subpopulation of CGRP-containing sensory neurons [12] where it seems to act as a prosensory neuropeptide [52].…”