Oosterwijk C, van Hulst K L, Visser C J, Woutersen R A, Lips C J, van den Tweel J G, Höppener J W
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Int J Cancer. 1997 Aug 7;72(4):637-41. doi: 10.1002/(sici)1097-0215(19970807)72:4<637::aid-ijc15>3.0.co;2-8.
Many patients with exocrine pancreatic cancer develop diabetes mellitus due to insulin resistance. This may relate to concurrent over-production of islet amyloid polypeptide (IAPP) by the pancreatic beta cells. We investigated the effects of pancreatic cancer on circulating IAPP and glucose homeostasis in azaserine-treated rats (developing acinar pancreatic tumours) and BOP-treated hamsters (developing ductular pancreatic tumours). Glucose, insulin and IAPP levels in plasma were neither affected in azaserine-only treated rats nor in animals with enhanced carcinogenesis after chronic caerulein treatment. Azaserine-treated rats on a high-fat diet had decreased insulin levels and enhanced IAPP/insulin ratios in plasma, without hyperglycaemia. All BOP-treated hamsters showed pancreatic carcinogenesis at 6 months post-treatment. Supranormal plasma glucose levels in animals on a low-fat diet were the only change observed. After a second 6-month period, subnormal plasma glucose levels, at least 4-fold decreased plasma insulin and up to 2-fold decreased plasma IAPP levels were present in all hamsters. Remarkably, both in azaserine-treated rats on high-fat and in BOP-treated hamsters, decreased insulin levels and elevated IAPP/insulin ratios are not associated with hyperglycaemia. In contrast to humans with pancreatic cancer, IAPP over-production and hyperglycaemia do not develop in rats and hamsters with (pre-)neoplastic pancreatic lesions.
许多外分泌性胰腺癌患者因胰岛素抵抗而患糖尿病。这可能与胰腺β细胞同时过度产生胰岛淀粉样多肽（IAPP）有关。我们研究了胰腺癌对用氮杂丝氨酸处理的大鼠（发生腺泡胰腺肿瘤）和用BOP处理的仓鼠（发生导管胰腺肿瘤）循环IAPP和葡萄糖稳态的影响。仅用氮杂丝氨酸处理的大鼠以及经慢性蛙皮素处理后致癌作用增强的动物，其血浆中的葡萄糖、胰岛素和IAPP水平均未受影响。高脂饮食的氮杂丝氨酸处理大鼠血浆胰岛素水平降低，IAPP/胰岛素比值升高，但无高血糖症。所有用BOP处理的仓鼠在处理后6个月均出现胰腺癌。低脂饮食动物中仅观察到血浆葡萄糖水平高于正常。在第二个6个月期间后，所有仓鼠均出现血浆葡萄糖水平低于正常、血浆胰岛素水平至少降低4倍以及血浆IAPP水平降低多达2倍的情况。值得注意的是，在高脂饮食的氮杂丝氨酸处理大鼠和用BOP处理的仓鼠中，胰岛素水平降低和IAPP/胰岛素比值升高均与高血糖症无关。与胰腺癌患者不同，患有（癌前）胰腺病变的大鼠和仓鼠不会出现IAPP过度产生和高血糖症。
