{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:22:13Z","timestamp":1783606933692,"version":"3.55.0"},"reference-count":40,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":144,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:p>Pancreatic neuroendocrine tumors (PanNETs) represent a rare subset of pancreatic cancers, comprising approximately 1\u20132% of all cases. Non-functioning PanNETs (NF-PanNETs), which account for the majority of PanNETs, can be difficult to treat as they show no hormone-related symptoms and are often not diagnosed until more advanced stages. Current therapeutic agents have limited efficacy, highlighting the need for novel treatment strategies. Multiple endocrine neoplasia type 1 is a hereditary syndrome strongly associated with PanNETs and pituitary neuroendocrine tumors (PitNETs), caused by germline mutations in the MEN1 gene. Using Men1f\/f\u2212RipCre+ mice, which develop both NF-PanNETs and PitNETs, we investigated whether long-term administration of metformin, a first-line anti-diabetic drug, could suppress tumor development and progression. Metformin significantly inhibited the elevation of blood glucose in Men1f\/f\u2212RipCre+ mice, and longer-term treatment attenuated PanNETs and restored normal insulin secretion. Metformin suppressed the proliferative pathways, including the PI3K\/Akt\/mTOR signaling pathway. In addition to its effects on PanNETs, metformin also attenuated PitNET development, elevated antiproliferative pathways, and suppressed angiogenic pathways. Furthermore, clinical data revealed that NF-PanNET patients with prior metformin use exhibited improved prognosis. These findings demonstrate that blood glucose control through metformin represents a promising preventive and therapeutic strategy for NF-PanNETs and MEN1-associated neuroendocrine tumors.<\/jats:p>","DOI":"10.1530\/erc-25-0518","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T10:25:55Z","timestamp":1769077555000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":1,"title":["Metformin suppresses MEN1-associated pancreatic and pituitary neuroendocrine tumors: evidence from mouse models and clinical 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