Aspirin and Diabetes: Inhibition of Amylin Aggregation by Nonsteroidal Anti-Inflammatory Drugs

Abstract

Islet amyloid polypeptide (amylin), cosecreted with insulin by the pancreatic β-cells, has an important role in the regulation of islet cell hormone homeoastasis. Deposition of β-sheet polypeptide fibrils into amyloid deposits is considered to be central to the pathology of a number of amyloidogenic disorders, including type-2 diabetes. Amyloid deposits comprised of β-sheet fibrillar amylin observed in type-2 diabetics are cytotoxic and may have a prominent role in causing β-cell dysfunction. The amyloidogenic process may impair β-cell function before cell death and replacement by amyloid. Preservation of β-cell viability and insulin secretion is a major objective in diabetic care. Using circular dichroism and Congo red absorption techniques we found that clinically relevant doses of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) prevented and also reversed the β-sheet conformation of human amylin. The specific COX-2 inhibitors were less effective. The anti-inflammatory steroid prednisolone or the analgesic acetaminophen had no effect on amylin fibrillogenesis. This action of NSAIDS was similar to their inhibition of β-sheet conformation of the Alzheimer protein, amyloid-β. Aspirin, currently recommended for the prevention of cardiovascular complications in diabetic patients, may also ameliorate the disease process in diabetes by preserving the β-cell function.

Key words

Amylin - Aspirin - NSAIDS - Amyoloid - COX-1 - COX-2

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