Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus.

The 37-amino-acid polypeptide amylin is the principal constituent of the amyloid deposits that form in the islets of Langerhans in patients with type-2 diabetes mellitus, but its role in the pathogenesis of this disease is unresolved. In view of the fact that the beta-amyloid protein that forms fibrils in Alzheimer's disease is toxic to neurons, we have investigated whether amylin fibrils could be toxic to pancreatic islet cells. We show here that human amylin is toxic to insulin-producing beta-cells of the adult pancreas of rats and humans.

A calcium-stimulated serine protease from monkey brain degrades the beta-amyloid precursor protein.

Amyloid deposition, a histopathological feature of Alzheimer's disease brain, may be the underlying cause of this disease. The isolation of enzymes involved in both the normal and aberrant or alternative processing of the beta-amyloid precursor protein may lead to an understanding of how beta-protein, the major component of amyloid deposits, is formed in the brain parenchyma and vasculature of Alzheimer's disease patients and aged humans. As the same kind of deposits is also found in aged primates, the use of primates will undoubtedly help to understand the mechanisms of amyloid deposition, both spatially and temporally.

Studies on the proteolytic degradation of the beta-protein precursor by proteases purified from Alzheimer's disease brain.

In Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of Dutch origin, and normal aging, amyloid accumulates in the brain parenchyma and blood vessels. The major protein in the deposits is the beta-protein, a 4-kD peptide possibly generated by an abnormal degradation of its precursor, the beta-protein precursor (beta PP). We found, as a second component of the brain amyloid, the serine protease inhibitor alpha 1-antichymotrypsin (ACT).