Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, CA 90024-2852, USA.
Diabetologia. 2010 Jan;53(1):21-6. doi: 10.1007/s00125-009-1556-8. Epub 2009 Oct 21.
AIMS/HYPOTHESIS: In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans.
We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI <25 kg/m(2)); obese (BMI >27 kg/m(2)); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication.
We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls.
CONCLUSIONS/INTERPRETATION: Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.
目的/假设：在 2 型糖尿病的高脂肪喂养大鼠模型中，我们注意到外分泌管复制增加。这是胰腺炎和胰腺癌的一个易感因素，这两种疾病在 2 型糖尿病中更为常见。本研究的目的是确定肥胖和/或 2 型糖尿病是否与人类胰腺导管复制增加有关。
我们从 45 名人类尸体中获得胰腺，分为四组：瘦（BMI<25kg/m²）；肥胖（BMI>27kg/m²）；非糖尿病；和 2 型糖尿病。用细胞角蛋白和 Ki67 等导管细胞标志物对胰腺进行免疫染色，以评估胰腺。
我们首次表明，肥胖和 2 型糖尿病在人类中都与胰腺导管复制增加有关。具体来说，我们报告（1）肥胖使胰腺导管细胞的复制增加了十倍，（2）与瘦的非糖尿病对照组相比，患有 2 型糖尿病的瘦受试者胰腺导管细胞的复制增加了四倍。
结论/解释：人类的胰腺导管细胞复制增加是对肥胖和 2 型糖尿病的反应，这可能为肥胖和/或 2 型糖尿病患者胰腺炎和胰腺癌风险增加提供了一种机制。
