{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:53:48Z","timestamp":1790171628657,"version":"4.1.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p> The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve \u03b2-cell mass. However, sitagliptin also increases \u03b2-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated \u03b2-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing \u03b2-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and \u03b2-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and\/or pancreatic metaplasia\/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, \u03b2-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced \u03b2-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates \u03b2-cell secretion without increasing amyloid formation and protects against amyloid-induced \u03b2-cell loss. This suggests a novel effect of sitagliptin to protect the \u03b2-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. <\/jats:p>","DOI":"10.1152\/ajpendo.00025.2013","type":"journal-article","created":{"date-parts":[[2013,6,5]],"date-time":"2013-06-05T05:57:39Z","timestamp":1370411859000},"page":"E475-E484","source":"Crossref","is-referenced-by-count":32,"title":["One year of sitagliptin treatment protects against islet amyloid-associated \u03b2-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice"],"prefix":"10.1152","volume":"305","author":[{"given":"Kathryn","family":"Aston-Mourney","sequence":"first","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington;"},{"name":"Metabolic Research Unit, School of Medicine, Deakin University, Victoria, Australia; 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