Aspirin and diabetes: inhibition of amylin aggregation by nonsteroidal anti-inflammatory drugs.
Islet amyloid polypeptide (amylin), cosecreted with insulin by the pancreatic beta-cells, has an important role in the regulation of islet cell hormone homeoastasis. Deposition of beta-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 beta-sheet fibrillar amylin observed in type-2 diabetics are cytotoxic and may have a prominent role in causing beta-cell dysfunction. The amyloidogenic process may impair beta-cell function before cell death and replacement by amyloid. Preservation of beta-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 beta-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 beta-sheet conformation of the Alzheimer protein, amyloid-beta. Aspirin, currently recommended for the prevention of cardiovascular complications in diabetic patients, may also ameliorate the disease process in diabetes by preserving the beta-cell function.
Thomas
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Woodlands Medical Center and Endron Therapeutics, Oldsmar, Florida 34677, USA. ayurveda.treatment@verizon.net
Nadackal
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Thomas
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D000682:Amyloid / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001241:Aspirin / Q000737:chemistry*; D002942:Circular Dichroism; D003224:Congo Red; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017433:Protein Structure, Secondary
D000682:Amyloid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D058228:Islet Amyloid Polypeptide; D007527:Isoenzymes; D008565:Membrane Proteins; D003224:Congo Red; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin