{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:59:14Z","timestamp":1793343554876,"version":"4.5.0"},"reference-count":141,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[1993,7,1]],"date-time":"1993-07-01T00:00:00Z","timestamp":741484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[1993,7]]},"abstract":"<jats:p>Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic \u03b2-cells and is co-packaged with insulin in the \u03b2-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the \u03b2-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretogogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)\u201389 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20\u201329 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical\/chemical damage to \u03b2-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of \u03b2-cells and\/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin-dependent diabetes mellitus and NIDDM is currently unknown.<\/jats:p>","DOI":"10.1177\/030098589303000401","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T17:19:33Z","timestamp":1268068773000},"page":"317-332","source":"Crossref","is-referenced-by-count":95,"title":["Islet Amyloid Polypeptide: A Review of Its Biology and Potential Roles in the Pathogenesis of Diabetes Mellitus"],"prefix":"10.1177","volume":"30","author":[{"given":"T. D.","family":"O'Brien","sequence":"first","affiliation":[{"name":"Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN"},{"name":"Endocrine Research Unit, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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