Prevention of pancreatic cancer induction in hamsters by metformin
Prevention of pancreatic cancer induction in hamsters by metformin
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DOI：
10.1053/gast.2001.23258
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发表时间：
2001-04-01
期刊：
影响因子：
29.4
通讯作者：
Pour, PM
中科院分区：
文献类型：
--
作者：
Schneider, MB;Matsuzaki, H;Pour, PM
背景和目标：我们以前的研究表明，已知的促进作用的高脂肪饮食，这在仓鼠诱导外周胰岛素抵抗，与胰岛细胞的代偿性增殖。本研究旨在探讨胰岛细胞增殖的抑制是否能抑制高脂饮食对胰腺癌发生的促进作用。方法：采用两组高脂喂养的仓鼠。其中一组给予蛋氨酸饮用水（HF+Met组），另一组作为对照组（HF组）。在预期血浆胰岛素水平正常化时，所有仓鼠均用胰腺致癌物N-亚硝基双-（2-氧代丙基）胺，并在42周后终止实验。虽然高脂组中有50%的仓鼠发生了恶性病变，但HF+Met组中没有发现（P <0.05）。此外，在高脂组（8.6个病变/仓鼠）中检测到的增生和癌前病变（其中大部分在胰岛内）显著多于HF+Met组（1.8个病变/仓鼠）。结论：这些结果进一步支持胰岛细胞在胰腺癌发生中的重要作用，并可能解释胰腺癌和肥胖之间的关系，肥胖通常与外周胰岛素抵抗有关。
Background & Aims: Our previous study suggested that the known promotional effect of a high fat diet, which in hamsters induces peripheral insulin resistance, is related to a compensatory proliferation of islet cells. The present study was to examine whether the prevention of islet cell proliferation can inhibit the promotional effect of a high-fat diet in pancreatic carcinogenesis. Methods: Two groups of high fat-fed hamsters were used. One group received Metformin in drinking water for life (HF+Met group), and the other group served as a control (HF group). At the time when the normalization of the plasma insulin level was expected, all hamsters were treated with the pancreatic carcinogen, N-nitrosobis-(2-oxopropyl)amine, and the experiment was terminated 42 weeks later, Results: Although 50% of the hamsters in the high-fat group developed malignant lesions, none was found in the HF+Met group (P < 0,05), Also, significantly more hyperplastic and premalignant lesions, most of which were found within the islets, were detected in the high-fat group (8.6 lesions/hamster) than in the HF+Met group (1.8 lesions/hamster). Conclusions: The results lend further support on the significant role of islet cells in pancreatic carcinogenesis and may explain the association between pancreatic cancer and obesity, which is usually associated with peripheral insulin resistance.